Cysteine cathepsin S processes leptin, inactivating its biological activity

Oliveira, Marcela; Assis, Diego M.; Paschoalin, Thaysa; Miranda, Antônio; Ribeiro, Eliane; Juliano, María A.; Brὂmme, Dieter; Christoffolete, Marcelo A.; Barros, Nilana M.T.; Carmona, Adriana K.

doi:10.1530/joe-12-0108

Cited by 10 publications

(6 citation statements)

References 57 publications

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“…There are specific details to highlight regarding the differences among cathepsins K, L, and S. CatS appeared to degrade the fibrin gel faster than the other proteases in this in vitro study, but it may not necessarily be a better fibrinolytic enzyme than plasmin in vivo ; there are pH dependent and environmental cofactors that must be considered, but this deserves further investigation since catS is unique among cysteine cathepsins in that it retains its activity at neutral pH [10, 34]. Additionally, cathepsin S was shown to be elevated in the plasma of patients with diabetes [35, 36], associated with wound healing and hemostatic abnormalities, and other cardiovascular diseases, which may be a biomarker for these diseases [29, 37, 38].…”

Section: Discussionmentioning

confidence: 99%

Human cathepsins K, L, and S: Related proteases, but unique fibrinolytic activity

Douglas

Lamothe

Singleton

et al. 2018

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Discussionmentioning

confidence: 99%

Human cathepsins K, L, and S: Related proteases, but unique fibrinolytic activity

Douglas

Lamothe

Singleton

et al. 2018

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Stimulatory roles in adipogenesis have also been described for cathepsin S and its expression levels were found to be significantly influenced by metabolic changes (see Taleb and Clement , 2007 for a review). Cathepsins K and S, but not L, were also found to degrade leptin in vitro , but only cathepsin S was able to do so at pH 7.4 (Oliveira et al , 2012 ).…”

Section: Cathepsin K In Adipogenesis and Obesitymentioning

confidence: 93%

Cathepsin K: a unique collagenolytic cysteine peptidase

Novinec

Lenarčič²

2013

Biological Chemistry

121

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Cathepsin K has emerged as a promising target for the treatment of osteoporosis in recent years. Initially identified as a papain-like cysteine peptidase expressed in high levels in osteoclasts, the important role of this enzyme in bone metabolism was highlighted by the finding that mutations in the CTSK gene cause the rare recessive disorder pycnodysostosis, which is characterized by severe bone anomalies. At the molecular level, the physiological role of cathepsin K is reflected by its unique cleavage pattern of type I collagen molecules, which is fundamentally different from that of other endogenous collagenases. Several cathepsin K inhibitors have been developed to reduce the excessive bone matrix degradation associated with osteoporosis, with the frontrunner odanacatib about to successfully conclude Phase 3 clinical trials. Apart from osteoclasts, cathepsin K is expressed in different cell types throughout the body and is involved in processes of adipogenesis, thyroxine liberation and peptide hormone regulation. Elevated activity of cathepsin K has been associated with arthritis, atherosclerosis, obesity, schizophrenia, and tumor metastasis. Accordingly, its activity is tightly regulated via multiple mechanisms, including competitive inhibition by endogenous macromolecular inhibitors and allosteric regulation by glycosaminoglycans. This review provides a state-of-the-art description of the activity of cathepsin K at the molecular level, its biological functions and the mechanisms involved in its regulation.

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“…Recent research has also identified a plethora of extracellular substrates for cathepsin S, including the basement membrane component nidogen-1 (115) , the epithelial sodium channel (116) , leptin (117) , and plasminogen (118) . Similar to cathepsins B and X, cathepsin S has also been found associated with the cell surface (119) .…”

Section: Cathepsin L-like Peptidasesmentioning

confidence: 99%

Papain-like peptidases: structure, function, and evolution

Novinec

Lenarčič²

2013

BioMolecular Concepts

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Papain-like cysteine peptidases are a diverse family of peptidases found in most known organisms. In eukaryotes, they are divided into multiple evolutionary groups, which can be clearly distinguished on the basis of the structural characteristics of the proenzymes. Most of them are endopeptidases; some, however, evolved into exopeptidases by obtaining additional structural elements that restrict the binding of substrate into the active site. In humans, papain-like peptidases, also called cysteine cathepsins, act both as non-specific hydrolases and as specific processing enzymes. They are involved in numerous physiological processes, such as antigen presentation, extracellular matrix remodeling, and hormone processing. Their activity is tightly regulated and dysregulation of one or more cysteine cathepsins can result in severe pathological conditions, such as cardiovascular diseases and cancer. Other organisms can utilize papainlike peptidases for different purposes and they are often part of host-pathogen interactions. Numerous parasites, such as Plasmodium and flukes, utilize papain-like peptidases for host invasion, whereas plants, in contrast, use these enzymes for host defense. This review presents a state-of-the-art description of the structure and phylogeny of papain-like peptidases as well as an overview of their physiological and pathological functions in humans and in other organisms.

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Cysteine cathepsin S processes leptin, inactivating its biological activity

Cited by 10 publications

References 57 publications

Human cathepsins K, L, and S: Related proteases, but unique fibrinolytic activity

Human cathepsins K, L, and S: Related proteases, but unique fibrinolytic activity

Cathepsin K: a unique collagenolytic cysteine peptidase

Papain-like peptidases: structure, function, and evolution

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