Displaying publications 1 - 20 of 46 in total

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  1. Fulltext Newcastle disease virus degrades HIF-1α through proteasomal pathways independent of VHL and p53
    Abd-Aziz N, Stanbridge EJ, Shafee N
    J Gen Virol, 2016 Dec;97(12):3174-3182.
    PMID: 27902314 DOI: 10.1099/jgv.0.000623
    Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated α (HIF-1α) and a constitutive β subunit (HIF-1β). To investigate the effects of NDV infection on HIF-1α in cancer cells, the osteosarcoma (Saos-2), breast carcinoma (MCF-7), colon carcinoma (HCT116) and fibrosarcoma (HT1080) cell lines were used in the present study. Data obtained showed that a velogenic NDV infection diminished hypoxia-induced HIF-1α accumulation, leading to a decreased activation of its downstream target gene, carbonic anhydrase 9. This NDV-induced downregulation of HIF-1α occurred post-translationally and was partially abrogated by proteasomal inhibition. The process appeared to be independent of the tumour suppressor protein p53. These data revealed a correlation between NDV infection and HIF-1α downregulation, which highlights NDV as a promising agent to eliminate hypoxic cancer cells.
    Matched MeSH terms: Proteolysis
  2. Isolation and characterization of pepsin-solubilized collagen from the integument of sea cucumber (Stichopus vastus)
    Abedin MZ, Karim AA, Ahmed F, Latiff AA, Gan CY, Che Ghazali F, et al.
    J Sci Food Agric, 2013 Mar 30;93(5):1083-8.
    PMID: 22936269 DOI: 10.1002/jsfa.5854
    Sea cucumber (Stichopus vastus) is considered an underutilized resource, since only its stomach and intestines are eaten raw as salad in a few countries and the remaining parts, especially the integument rich in collagen, is discarded. Hence a valuable by-product having potential nutraceutical and pharmaceutical applications is wasted. In the present investigation, pepsin-solubilized collagen (PSC) from the integument of S. vastus was isolated, purified and characterized.
    Matched MeSH terms: Proteolysis
  3. Structure-informed separation of bioactive peptides
    Acquah C, Chan YW, Pan S, Agyei D, Udenigwe CC
    J Food Biochem, 2019 01;43(1):e12765.
    PMID: 31353493 DOI: 10.1111/jfbc.12765
    The application of proteomic and peptidomic technologies for food-derived bioactive peptides is an emerging field in food sciences. These technologies include the use of separation tools coupled to a high-resolution spectrometric and bioinformatic tools for prediction, identification, sequencing, and characterization of peptides. To a large extent, one-dimensional separation technologies have been extensively used as a continuous tool under different optimized conditions for the identification and analysis of food peptides. However, most one-dimensional separation technologies are fraught with significant bottlenecks such as insufficient sensitivity and specificity limits for complex samples. To address this limitation, separation systems based on orthogonal, multidimensional principles, which allow for the coupling of more than one analytical separation tool with different operational principles, provide a higher separation power than one-dimensional separation tools. This review describes the structure-informed separation and purification of protein hydrolyzates to obtain peptides with desirable bioactivities. PRACTICAL APPLICATIONS: Application of bioactive peptides in the formulation of functional foods, nutraceuticals, and therapeutic agents have increasingly gained scholarly and industrial attention. The bioactive peptides exist originally in protein sources and are only active after hydrolysis of the parent protein. Currently, several tools can be configured in one-dimensional or multidimensional systems for the separation and purification of protein hydrolyzates. The separations are informed by the structural properties such as the molecular weight, charge, hydrophobicity or hydrophilicity, and the solubility of peptides. This review provides a concise discussion on the commonly used analytical tools, their configurations, advantages and challenges in peptide separation. Emphasis is placed on how the structural properties of peptides assist in the separation and purification processes and the concomitant effect of the separation on peptide bioactivity.
    Matched MeSH terms: Proteolysis
  4. Fulltext Myofibrillar protein profile of Pectoralis major muscle in broiler chickens subjected to different freezing and thawing methods
    Adeyemi, K.D., Mislan, N., Aghwan, Z.A., Sarah, S.A., Sazili, A.Q.
    International Food Research Journal, 2014;21(3):1125-1129.
    MyJurnal
    The study examined the protein profile of Pectoralis major muscle in broiler chickens subjected to different freezing and thawing methods. Pectoralis major muscle was excised from the carcasses of twenty broiler chickens and split into left and right halves. The left half was subjected to slow freezing (-20oC) while the right half was rapidly frozen (-80oC). The samples were stored at their respective temperature for 2 weeks and assigned to either of tap water (27oC, 30 min), room temperature (26oC, 60 min), microwave (750W, 10 min) or chiller (4oC, 6 h) thawing. Changes in myofibrillar proteins following the thawing methods were monitored through sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The electrophoretic profile indicated differences (p < 0.05) in intensities of the components of myofibrillar proteins among the thawing methods in both slow and rapidly frozen samples. Chiller thawing had significantly higher (p < 0.05) protein concentration than other methods in rapidly frozen samples. However, in slow freezing, there were no significant differences in protein concentration among the thawing methods. In rapidly frozen samples, the protein optical densities at molecular weight of 21, 27, 55 and 151kDa in tap water, chiller and room temperature thawing did not differ (p < 0.05). Similarly, in slowly frozen samples, protein optical densities at molecular weight of 21, 27, 85 and 151 kDa were not significantly different among chill, tap water and room temperature thawing. Microwave thawing consistently caused higher protein degradation resulting in significantly lower (p < 0.05) protein quality and quantity in both freezing methods.
    Matched MeSH terms: Proteolysis
  5. Viability and activity of bifidobacteria during refrigerated storage of yoghurt containing Mangifera pajang fibrous polysaccharides
    Al-Sheraji SH, Ismail A, Manap MY, Mustafa S, Yusof RM
    J Food Sci, 2012 Nov;77(11):M624-30.
    PMID: 23106104 DOI: 10.1111/j.1750-3841.2012.02955.x
    The viability and activity of Bifidobacterium pseudocatenulatum G4, B. longum BB 536 and yoghurt cultures (Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus) were studied in yoghurt containing 0.75% Mangefira pajang fibrous polysaccharides (MPFP) and inulin. Growth of probiotic organisms, their proteolytic activities, the production of short chain fatty acids (lactic, acetic and propionic) and the pH of the yoghurt samples were determined during refrigerated storage at 4 °C for 28 d. B. pseudocatenulatum G4 and B. longum BB 536 showed better growth and activity in the presence of MPFP and inulin, which significantly increased the production of short chain fatty acids as well as the proteolytic activity of these organisms.
    Matched MeSH terms: Proteolysis
  6. Fulltext Optimizing the acceleration of Cheddar cheese ripening using response surface methodology by microbial protease without altering its quality features
    Alhelli AM, Mohammed NK, Khalil ES, Hussin ASM
    AMB Express, 2021 Mar 22;11(1):45.
    PMID: 33751265 DOI: 10.1186/s13568-021-01205-9
    Cheddar cheese proteolysis were accelerated employing Penicillium candidum PCA1/TT031 protease into cheese curd. In the present study, several of the significant factors such as protease purification factor (PF), protease concentration and ripening time were optimized via the response surface methodology (RSM). The ideal accelerated Cheddar cheese environment consisted of 3.12 PF, 0.01% (v/v) protease concentration and 0.6/3 months ripening time at 10 °C. The RSM models was verified to be the most proper methodology for the maintain of chosen Cheddar cheese. Under this experimental environment, the pH, acid degree value (ADV), moisture, water activity (aw), soluble nitrogen (SN)%, fat and overall acceptability were found to be 5.4, 6.6, 35%, 0.9348, 18.8%, 34% and 13.6, respectively of ideal Cheddar cheese. Furthermore, the predicted and experimental results were in significant agreement, which confirmed the validity and reliability of the suggested method. In spite of the difference between the ideal and commercial Cheddar cheese in the concentration of some of amino acids and free fatty acids, the sensory evaluation did not show any significant difference in aroma profile between them.
    Matched MeSH terms: Proteolysis
  7. Helicobacter pylori protein HP0986 (TieA) interacts with mouse TNFR1 and triggers proinflammatory and proapoptotic signaling pathways in cultured macrophage cells (RAW 264.7)
    Ansari SA, Devi S, Tenguria S, Kumar A, Ahmed N
    Cytokine, 2014 Aug;68(2):110-7.
    PMID: 24767863 DOI: 10.1016/j.cyto.2014.03.006
    HP0986 protein of Helicobacter pylori has been shown to trigger induction of proinflammatory cytokines (IL-8 and TNF-α) through the activation of NF-κB and also to induce Fas mediated apoptosis of human macrophage cells (THP-1). In this study, we unravel mechanistic details of the biological effects of this protein in a murine macrophage environment. Up regulation of MCP-1 and TNF-α in HP0986-induced RAW 264.7 cells occurred subsequent to the activation and translocation of NF-κB to the cell nucleus. Further, HP0986 induced apoptosis of RAW 264.7 cells through Fas activation and this was in agreement with previous observations made with THP-1 cells. Our studies indicated activation of TNFR1 through interaction with HP0986 and this elicited the aforementioned responses independent of TLR2, TLR4 or TNFR2. We found that mouse TNFR1 activation by HP0986 facilitates formation of a complex comprising of TNFR1, TRADD and TRAF2, and this occurs upstream of NF-κB activation. Furthermore, FADD also forms a second complex, at a later stage, together with TNFR1 and TRADD, resulting in caspase-8 activation and thereby the apoptosis of RAW 264.7 cells. In summary, our observations reveal finer details of the functional activity of HP0986 protein in relation to its behavior in a murine macrophage cell environment. These findings reconfirm the proinflammatory and apoptotic role of HP0986 signifying it to be an important trigger of innate responses. These observations form much needed baseline data entailing future in vivo studies of the functions of HP0986 in a murine model.
    Matched MeSH terms: Proteolysis
  8. Anaerobic respiration: In vitro efficacy of Nitazoxanide against mitochondriate Acanthamoeba castellanii of the T4 genotype
    Aqeel Y, Siddiqui R, Farooq M, Khan NA
    Exp Parasitol, 2015 Oct;157:170-6.
    PMID: 26297676 DOI: 10.1016/j.exppara.2015.08.007
    Acanthamoeba is an opportunistic protist pathogen that is responsible for serious human and animal infection. Being one of the most frequently isolated protists from the environment, it is likely that it readily encounters microaerophilic environments. For respiration under anaerobic or low oxygen conditions in several amitochondriate protists, decarboxylation of pyruvate is catalyzed by pyruvate ferredoxin oxidoreductase instead of pyruvate dehydrogenase. In support, Nitazoxanide, an inhibitor of pyruvate ferredoxin oxidoreductase, is effective and non-mutagenic clinically against a range of amitochondriate protists, Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. The overall aim of the present study was to determine in vitro efficacy of Nitazoxanide against Acanthamoeba castellanii. At micromolar concentrations, the findings revealed that Nitazoxanide neither affected A. castellanii growth or viability nor amoeba-mediated host cell monolayer damage in vitro or extracellular proteolytic activities. Similarly, microaerophilic conditions alone had no significant effects. In contrast, microaerophilic conditions together with Nitazoxanide showed amoebicidal effects and inhibited A. castellanii-mediated host cell monolayer damage as well as extracellular proteases. Using encystation assays, it was observed that Nitazoxanide inhibited trophozoite transformation into cysts both under aerophilic and microaerophilic conditions. Furthermore, pre-treatment of cysts with Nitazoxanide inhibited A. castellanii excystation. These findings are important in the identification of potential targets that could be useful against parasite-specific respiration as well as to understand the basic biology of the life cycle of Acanthamoeba.
    Matched MeSH terms: Proteolysis/drug effects
  9. The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation
    Bhowmick S, Chakravarty C, Sellathamby S, Lal SK
    Arch Virol, 2017 Apr;162(4):919-929.
    PMID: 27942972 DOI: 10.1007/s00705-016-3153-8
    The matrix protein 2 (M2) is a spliced product of segment 7 genome of influenza A virus. Previous studies indicate its role in uncoating of the viral ribonucleoprotein complex during viral entry and in membrane scission while budding. Despite its crucial role in the viral life cycle, little is known about its subcellular distribution and dynamics. In this study, we have shown that the M2 protein is translocated from the membrane to the cytoplasm by a retrograde route via endosomes and the Golgi network. It utilizes retromer cargo while moving from the endosome to the trans-Golgi network and prevents endosome fusion with the lysosome. Further, M2 interacts with the endoplasmic-reticulum-resident AAA-ATPase p97 for its release into the cytoplasm. Our study also revealed that the M2 protein in the cellular milieu does not undergo ubiquitin-mediated proteasomal degradation. The migration of M2 through this pathway inside the infected cell suggests possible new roles that the M2 protein may have in the host cytoplasm, apart from its previously described functions.
    Matched MeSH terms: Proteolysis
  10. Fulltext The improvement of the endogenous antioxidant property of stone fish (Actinopyga lecanora) tissue using enzymatic proteolysis
    Bordbar S, Ebrahimpour A, Abdul Hamid A, Abdul Manap MY, Anwar F, Saari N
    Biomed Res Int, 2013;2013:849529.
    PMID: 23586061 DOI: 10.1155/2013/849529
    The stone fish (Actinopyga lecanora) ethanolic and methanolic tissue extracts were investigated for total phenolic contents (TPCs) as well as antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) radical scavenging activity and ferric reducing antioxidant power (FRAP) assays. Both extracts showed low amount of phenolics (20.33 to 17.03 mg of gallic acid equivalents/100 g dried sample) and moderate antioxidant activity (39% to 34% DPPH(•) radical scavenging activity and 23.95 to 22.30 mmol/100 mL FeSO4 FRAP value). Enzymatic proteolysis was carried out in order to improve the antioxidant activity using six commercially available proteases under their optimum conditions. The results revealed that the highest increase in antioxidant activity up to 85% was obtained for papain-generated proteolysate, followed by alcalase (77%), trypsin (75%), pepsin (68%), bromelain (68%), and flavourzyme (50%) as measured by DPPH(•) radical scavenging activity, whilst for the FRAP value, the highest increase in the antioxidant activity up to 39.2 mmol/100 mL FeSO4 was obtained for alcalase-generated proteolysate, followed by papain (29.5 mmol/100 mL FeSO4), trypsin (23.2 mmol/100 mL FeSO4), flavourzyme (24.7 mmol/100 mL FeSO4), bromelain (22.9 mmol/100 mL FeSO4), and pepsin (20.8 mmol/100 mL FeSO4). It is obvious that proteolysis of stone fish tissue by proteolytic enzymes can considerably enhance its antioxidant activity.
    Matched MeSH terms: Proteolysis*
  11. Fulltext Rapid isolation of genomic DNA from Asian green-lipped mussel (Perna viridis) for random amplified microsatellite polymorphism
    Chai, L.C., Fatimah, C.A., Norhisyam, M.S., Rozila, A., Nadzirah, A.S., Natasha, L.H.Y.
    International Food Research Journal, 2009;16(1):113-118.
    MyJurnal
    The objective of the present study was to develop a rapid, reliable and yet inexpensive protocol for genomic DNA extraction from frozen and ethanol-preserved Asian green-lipped mussels for random amplified microsatelite (RAM) analysis. The procedure comprised of three major steps: (1) Tissue degradation by boiling in 6% Chelex 100 resin in TE buffer; (2) Protein digestion by Proteinase K; and (3) DNA precipitation by adding 2 volumes of cold absolute ethanol. The entire procedure can be completed within two hours. The resulting RAM profiles were clear and reproducible. Our results demonstrate that the combined protocol of Chelex 100-Proteinase K-ethanol precipitation is a powerful yet economical DNA isolation method for population genetic studies involving a large sample size.
    Matched MeSH terms: Proteolysis
  12. Proteomic analysis reveals that treatment with tocotrienols reverses the effect of H₂O₂ exposure on peroxiredoxin expression in human lymphocytes from young and old individuals
    Dahlan HM, Karsani SA, Rahman MA, Hamid NA, Top AG, Ngah WZ
    J Nutr Biochem, 2012 Jul;23(7):741-51.
    PMID: 21840697 DOI: 10.1016/j.jnutbio.2011.03.018
    Vitamin E has been suggested to modulate age-associated changes by altering the redox balance resulting in altered gene and/or protein expression. Here we have utilized proteomics to determine whether such regulation in protein expression occurs in human lymphocytes from two different age groups stressed with H₂O₂ and then treated with vitamin E in the form of tocotrienol-rich fraction (TRF). In this study, lymphocytes obtained from young (30-49 years old) and old (>50 years old) volunteers were first challenged with 1 mM H₂O₂. They were then treated by exposure to 50, 100 and 200 μg/ml TRF. Two-dimensional gel electrophoresis followed by MALDI-TOF/TOF (matrix-assisted laser desorption/ionization time-of-flight/time-of-flight) tandem mass spectrometry was then performed on whole-cell protein extracts to identify proteins that have changed in expression. A total of 24 proteins were found to be affected by H₂O₂ and/or TRF treatment. These included proteins that were related to metabolism, antioxidants, structural proteins, protein degradation and signal transduction. Of particular interest was the regulation of a number of proteins involved in stress response--peroxiredoxin-2, peroxiredoxin-3 and peroxiredoxin-6-all of which were shown to be down-regulated with H₂O₂ exposure. The effect was reversed following TRF treatment. The expression of peroxiredoxin-2 and peroxiredoxin-6 was confirmed by quantitative reverse transcriptase polymerase chain reaction. These results suggested that TRF directly influenced the expression dynamics of the peroxiredoxin-2, thus improving the cells ability to resist damage caused by oxidative stress.
    Matched MeSH terms: Proteolysis/drug effects
  13. Microsporum fulvum IBRL SD3: as novel isolate for chicken feathers degradation
    Darah I, Nur-Diyana A, Nurul-Husna S, Jain K, Lim SH
    Appl Biochem Biotechnol, 2013 Dec;171(7):1900-10.
    PMID: 24013862 DOI: 10.1007/s12010-013-0496-4
    Keratinous wastes have increasingly become a problem and accumulate in the environment mainly in the form of feathers, generated mainly from a large number of poultry industries. As keratins are very difficult to degrade by general proteases, they pose a major environmental problem. Therefore, microorganisms which would effectively degrade keratins are needed for recycling such wastes. A geophilic dermatophyte, Microsporum fulvum IBRL SD3 which was isolated from a soil sample collected from a chicken feather dumping site using a baiting technique, was capable to produce keratinase significantly. The crude keratinase was able to degrade whole chicken feathers effectively. The end product of the degradation was protein that contained essential amino acids and may have potential application in animal feed production. Thus, M. fulvum could be a novel organism to produce keratinase for chicken feathers degradation.
    Matched MeSH terms: Proteolysis*
  14. Fulltext Kinetic characterization of Channa striatus muscle sarcoplasmic and myofibrillar protein hydrolysates
    Ghassem M, Fern SS, Said M, Ali ZM, Ibrahim S, Babji AS
    J Food Sci Technol, 2014 Mar;51(3):467-75.
    PMID: 24587521 DOI: 10.1007/s13197-011-0526-6
    This study was conducted to evaluate the kinetic characteristics of proteolytic activity of proteases on Channa striatus protein fractions. Degree of hydrolysis (DH), amino acid composition and kinetic parameters of sarcoplasmic and myofibrillar proteins were investigated when incubated with proteinase K and thermolysin, separately. After 30 min incubation with proteases, a decrease in DH of sarcoplasmic protein was observed whereas, hydrolysis of myofibrillar protein with proteases took 2 h with an increase in DH. The major amino acids were glutamic acid (16.6%) in thermolysin- myofibrillar hydrolysate followed by aspartic acid (11.1%) in sarcoplasmic protein fraction with no enzyme treatment and lysine (10%) in thermolysin-myofibrillar hydrolysate. The apparent Michaelis constant of proteinase K was lower than thermolysin for both sarcoplasmic and myofibrillar proteins. However, rate of turnover and enzyme efficiency suggested that sarcoplasmic and myofibrillar proteins are suitable substrates for proteinase K and thermolysin hydrolytic reaction, respectively.
    Matched MeSH terms: Proteolysis
  15. Properties of immobilized Candida Antarctica lipase B on highly macroporous copolymer
    Handayani N, Achmad S, Miletic N, Loos K, Wahyuningrum D
    Sains Malaysiana, 2011;40.
    In spite of their excellent catalytic properties, enzymes should be improved before their implementation both in industrial and laboratorium scales. Immobilization of enzyme is one of the ways to improve their properties. Candida antarctica lipase B (Cal-B) has been reported in numerous publications to be a particularly useful enzyme catalizing in many type of reaction including regio- and enantio- synthesis. For this case, cross-linking of immobilized Cal-B with 1,2,7,8 diepoxy octane is one of methods that proved significantly more stable from denaturation by heat, organic solvents, and proteolysis than lyophilized powder or soluble enzymes. More over, the aim of this procedure is to improve the activity and reusability of lipase. Enzyme kinetics test was carried out by transesterification reaction between 4-nitrophenyl acetate (pNPA) and methanol by varying substrate concentrations, and the result is immobilized enzymes follows the Michaelis-Menten models and their activity is match with previous experiment. Based on the Vmax values, the immobilized enzymes showed higher activity than the free enzyme. Cross-linking of immobilized lipase indicate that cross-linking by lower concentration of cross-linker, FIC (immobilized lipase that was incubated for 24 h) gave the highest activity and cross-linking by higher concentration of cross-linker, PIC (immobilized lipase that was incubated for 2 h) gives the highest activity. However, pore size and saturation level influenced their activity.
    Matched MeSH terms: Proteolysis
  16. Interventions of two-stage thermal sous-vide cooking on the toughness of beef semitendinosus
    Ismail I, Hwang YH, Joo ST
    Meat Sci, 2019 Nov;157:107882.
    PMID: 31295690 DOI: 10.1016/j.meatsci.2019.107882
    This paper describes the influence of different factors on toughness of beef semitendinosus (ST) by means of low temperature-long time cooking with single-stage (60 °C, 65 °C, 70 °C, and 75 °C for 6 h and 12 h) and two-stage sous-vide procedure (45 + 60 °C, 45 + 65 °C, 45 + 70 °C, and 45 + 75 °C; 49 + 60 °C, 49 + 65 °C, 49 + 70 °C, and 49 + 75 °C for 3 h at the first temperature, and either 3 or 9 h at the second temperature). Reduced toughness of ST beef steak muscle could be attained in 6 h at 60 °C and 45 + 60 °C were due from the minimum shrinkage of sarcomere as well as lower perimysial thickness, cooking loss, and elastic modulus. Collagen solubility showed a positive correlation to the toughness values. The relationship between proteolytic activity and shear force can be seen after 12 h of cooking duration. For the other quality attributes, two stepped cooking temperature-time combination seems to be more effective in preserving the redness values and water content than a single-stage sous-vide method.
    Matched MeSH terms: Proteolysis
  17. Fulltext The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues
    Kar R, Jha SK, Ojha S, Sharma A, Dholpuria S, Raju VSR, et al.
    Cancer Rep (Hoboken), 2021 08;4(4):e1369.
    PMID: 33822486 DOI: 10.1002/cnr2.1369
    BACKGROUND: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer.

    RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like βTrcP1 and βTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis.

    CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.

    Matched MeSH terms: Proteolysis
  18. Endosomal-lysosomal dysfunctions in Alzheimer's disease: Pathogenesis and therapeutic interventions
    Lai SSM, Ng KY, Koh RY, Chok KC, Chye SM
    Metab Brain Dis, 2021 08;36(6):1087-1100.
    PMID: 33881723 DOI: 10.1007/s11011-021-00737-0
    The endosomal-lysosomal system mediates the process of protein degradation through endocytic pathway. This system consists of early endosomes, late endosomes, recycling endosomes and lysosomes. Each component in the endosomal-lysosomal system plays individual crucial role and they work concordantly to ensure protein degradation can be carried out functionally. Dysregulation in the endosomal-lysosomal system can contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). In AD endosomal-lysosomal abnormalities are the earliest pathological features to note and hence it is important to understand the involvement of endosomal-lysosomal dysfunction in the pathogenesis of AD. In-depth understanding of this dysfunction can allow development of new therapeutic intervention to prevent and treat AD.
    Matched MeSH terms: Proteolysis
  19. Fulltext Comparative Study of Extracellular Proteolytic, Cellulolytic, and Hemicellulolytic Enzyme Activities and Biotransformation of Palm Kernel Cake Biomass by Lactic Acid Bacteria Isolated from Malaysian Foods
    Lee FH, Wan SY, Foo HL, Loh TC, Mohamad R, Abdul Rahim R, et al.
    Int J Mol Sci, 2019 Oct 09;20(20).
    PMID: 31600952 DOI: 10.3390/ijms20204979
    Biotransformation via solid state fermentation (SSF) mediated by microorganisms is a promising approach to produce useful products from agricultural biomass. Lactic acid bacteria (LAB) that are commonly found in fermented foods have been shown to exhibit extracellular proteolytic, β-glucosidase, β-mannosidase, and β-mannanase activities. Therefore, extracellular proteolytic, cellulolytic, and hemicellulolytic enzyme activities of seven Lactobacillus plantarum strains (a prominent species of LAB) isolated from Malaysian foods were compared in this study. The biotransformation of palm kernel cake (PKC) biomass mediated by selected L. plantarum strains was subsequently conducted. The results obtained in this study exhibited the studied L. plantarum strains produced versatile multi extracellular hydrolytic enzyme activities that were active from acidic to alkaline pH conditions. The highest total score of extracellular hydrolytic enzyme activities were recorded by L. plantarum RI11, L. plantarum RG11, and L. plantarum RG14. Therefore, they were selected for the subsequent biotransformation of PKC biomass via SSF. The hydrolytic enzyme activities of treated PKC extract were compared for each sampling interval. The scanning electron microscopy analyses revealed the formation of extracellular matrices around L. plantarum strains attached to the surface of PKC biomass during SSF, inferring that the investigated L. plantarum strains have the capability to grow on PKC biomass and perform synergistic secretions of various extracellular proteolytic, cellulolytic, and hemicellulolytic enzymes that were essential for the effective biodegradation of PKC. The substantial growth of selected L. plamtraum strains on PKC during SSF revealed the promising application of selected L. plantarum strains as a biotransformation agent for cellulosic biomass.
    Matched MeSH terms: Proteolysis
  20. Probing the endogenous peptidomes of cancer for biomarkers: A new endeavor
    Lee PY, Low TY, Jamal R
    Adv Clin Chem, 2018 12 27;88:67-89.
    PMID: 30612607 DOI: 10.1016/bs.acc.2018.10.004
    The life span of cancer patients can be prolonged with appropriate therapies if detected early. Mass screening for early detection of cancer, however, requires sensitive and specific biomarkers obtainable from body fluids such as blood or urine. To date, most biomarker discovery programs focus on the proteome rather than the endogenous peptidome. It has been long-established that tumor cells and stromal cells produce tumor resident proteases (TRPs) to remodel the surrounding tumor microenvironment in support of tumor progression. In fact, proteolytic products of TRPs have been shown to correlate with malignant behavior. Being of low molecular weight, these unique peptides can pass through the endothelial barrier of the vasculature into the bloodstream. As such, the cancer peptidome has increasingly become a focus for biomarker discovery. In this review, we discuss on the various aspects of the peptidome in cancer biomarker research.
    Matched MeSH terms: Proteolysis
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