Nomenclature: protease, proteinase and peptidase

Barrett, Alan J.; McDonald, J. Ken

doi:10.1042/bj2370935

Cited by 86 publications

(38 citation statements)

References 4 publications

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“…Cystatins control proteases by the formation of reversible high affinity complexes (Barrett and McDonald, 1986; Alvarez-Fernandez et al, 1999). The cystatin family comprises of at least seven different members i.e., the cystatins C, D, E/M, F and the salivary cystatins S, SA and SN.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer

Veena

Lee

Keppler

et al. 2008

Genes Chromosomes & Cancer

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We have previously localized a cervical cancer tumor suppressor gene to a 300 kb interval of 11q13. Analysis of candidate genes revealed loss of expression of cystatin E/M, a lysosomal cysteine protease inhibitor, in 6 cervical cancer cell lines and 9 of 11 primary cervical tumors. Examination of the three exons in four cervical cancer cell lines, 19 primary tumors, and 21 normal controls revealed homozygous deletion of exon 1 sequences in one tumor. Point mutations were observed in six other tumors. Two tumors contained mutations at the consensus binding sites for cathepsin L, a lysosomal protease over-expressed in cervical cancer. Introduction of these two point mutations using site directed mutagenesis resulted in reduced binding of mutated cystatin E/M to cathepsin L. Although mutations were not observed in any cell lines, four cell lines and 12 of 18 tumors contained promoter hypermethylation. Re-expression of cystatin E/M was observed after 5′aza 2-deoxycytidiene and/or Trichostatin A treatment of cervical cancer cell lines, HeLa and SiHa, confirming promoter hypermethylation. Ectopic expression of cystatin E/M in these two cell lines resulted in growth suppression. There was also suppression of soft agar colony formation by HeLa cells expressing the cystatin E/M gene. Re-expression of cystatin E/M resulted in decreased intracellular and extracellular expression of cathepsin L. Over-expression of cathepsin L resulted in increased cell growth which was inhibited by the reintroduction of cystatin E/M. We conclude, therefore, that cystatin E/M is a cervical cancer suppressor gene and that the gene is inactivated by somatic mutations and promoter hypermethylation.

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Section: Discussionmentioning

confidence: 99%

Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer

Veena

Lee

Keppler

et al. 2008

Genes Chromosomes & Cancer

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“…The analysis of the tick proteolytic pathway included the genes/proteins annotated as protease, proteinase, peptidase, and its inhibitors [41]. …”

Section: Methodsmentioning

confidence: 99%

The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

et al. 2016

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BackgroundThe intracellular bacteria Anaplasma phagocytophilum are emerging zoonotic pathogens affecting human and animal health, and a good model for the study of tick-host-pathogen interactions. This tick-borne pathogen is transmitted by Ixodes scapularis in the United States where it causes human granulocytic anaplasmosis. Tick midguts and salivary glands play a major role during tick feeding and development, and in pathogen acquisition, multiplication and transmission. Vertebrate host proteins are found in tick midguts after feeding and have been described in the salivary glands of fed and unfed ticks, suggesting a role for these proteins during tick feeding and development. Furthermore, recent results suggested the hypothesis that pathogen infection affects tick metabolic processes to modify host protein digestion and persistence in the tick with possible implications for tick physiology and pathogen life-cycle.MethodsTo address this hypothesis, herein we used I. scapularis female ticks fed on uninfected and A. phagocytophilum-infected sheep to characterize host protein content in midguts and salivary glands by proteomic analysis of tick tissues.ResultsThe results evidenced a clear difference in the host protein content between tick midguts and salivary glands in response to infection suggesting that A. phagocytophilum selectively manipulates the levels of vertebrate host proteins in ticks in a tissue-specific manner to facilitate pathogen infection, multiplication and transmission while preserving tick feeding and development. The mechanisms by which A. phagocytophilum manipulates the levels of vertebrate host proteins are not known, but the results obtained here suggested that it might include the modification of proteolytic pathways.ConclusionsThe results of this study provided evidence to support that A. phagocytophilum affect tick proteolytic pathways to selectively manipulate the levels of vertebrate host proteins in a tissue-specific manner to increase tick vector capacity. Investigating the biological relevance of host proteins in tick biology and pathogen infection and the mechanisms used by A. phagocytophilum to manipulate host protein content is essential to advance our knowledge of tick-host-pathogen molecular interactions. These results have implications for the identification of new targets for the development of vaccines for the control of tick-borne diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1747-3) contains supplementary material, which is available to authorized users.

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“…How these modified peptides contribute to the pathogenesis of AD is not precisely known yet, but their altered characteristics as compared to A 1-40/42 hold important clues. Cyclization of an Nterminal Glu renders peptides resistance against most extracellular aminopeptidase except the pGlu specific ones [106]. Another consequence of pGlu modification is the loss of one positive and two negative charges.…”

Section: Pyroglutamate Modified Amentioning

confidence: 99%

From Alpha to Omega with Aβ: Targeting the Multiple Molecular Appearances of the Pathogenic Peptide in Alzheimers Disease

Kimpe¹,

Scheper²

2010

CMC

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Amyloid beta (Abeta) is the main component of one of the major pathological hallmarks of Alzheimer's disease and is generally considered as one of the earliest factors that induce the pathogenic cascade. Abeta is produced from a larger precursor protein through proteolytic cleavage by secretase activities, which results in fragments that differ in size depending on the cleavage site used to create the C-terminus. In addition, heterogeneity at the N-terminus is created by proteases/peptidases. Moreover, various amino acid modifications further enhance the heterogeneity of Abeta that accumulates in Alzheimer brain. All these species with their different N-and C termini, with or without modifications have different aggregation properties. Abeta requires an aggregated state to be pathogenic and the exact aggregation state is a major determinant of the cellular effects of Abeta: smaller oligomeric aggregates are more neurotoxic, whereas large fibrillar aggregates are generally more associated with a glial response. It is therefore increasingly clear that Abeta is not a single entity, but a peptide with multiple molecular appearances. In this review we will discuss the mechanisms leading to the generation of the different Abeta species and their involvement in Alzheimer pathogenesis. This will be discussed in the framework of therapeutic approaches that target one of the steps in the biogenesis of toxic Abeta species: inhibition of the formation of Abeta, inhibition of aggregation and stimulation of its degradation or clearance.

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Nomenclature: protease, proteinase and peptidase

Cited by 86 publications

References 4 publications

Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer

Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer

The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

From Alpha to Omega with Aβ: Targeting the Multiple Molecular Appearances of the Pathogenic Peptide in Alzheimers Disease

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Nomenclature: protease, proteinase and peptidase

Cited by 86 publications

References 4 publications

Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer

Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer

The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

From Alpha to Omega with A&#946;: Targeting the Multiple Molecular Appearances of the Pathogenic Peptide in Alzheimers Disease

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From Alpha to Omega with Aβ: Targeting the Multiple Molecular Appearances of the Pathogenic Peptide in Alzheimers Disease