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Psoriatic epidermis is associated with upregulation of CDK 2 and inhibition of CDK 4 activity
Author(s) -
Henri P.,
Prevel C.,
Pellerano M.,
Lacotte J.,
Stoebner P.E.,
Morris M.C.,
Meunier L.
Publication year - 2020
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.18178
Subject(s) - cyclin dependent kinase , cyclin dependent kinase 2 , cyclin d1 , epidermis (zoology) , cancer research , cyclin , cyclin e , microbiology and biotechnology , kinase , cyclin a , cyclin d , biology , psoriasis , cell cycle , chemistry , protein kinase a , immunology , biochemistry , cell , anatomy
Summary Background The cyclin‐dependent kinases ( CDK s) CDK 2 and CDK 4 are involved in regulation of cell‐cycle progression, and psoriasis is characterized by hyperproliferation of basal epidermal cells. CDK inhibitory proteins ( CKI s) such as p16 INK 4A (p16) bind CDK 4/6 kinases and prevent their interaction with D‐type cyclins. CKI s such as p21 Cip1 (p21) and p27 Kip1 (p27) associate with CDK –cyclin complexes and prevent their activation. Objectives To gain insight into the molecular implication of CDK 2 and CDK 4 kinases in psoriasis, we sought to characterize expression of these kinases and associated cyclins, as well as of CKI s, and addressed the status of CDK 2 and CDK 4 activity in human psoriatic epidermis. Methods A cohort of 24 patients with psoriasis participated in the study. Biopsies were removed from a chronic plaque and from nonlesional skin. CDK 2, CDK 4, cyclin D1, cyclin E and CKI protein expression was assessed by immunoblotting, immunohistochemistry and immunofluorescence. CDK 4 and CDK 2 mRNA expression was determined by real‐time polymerase chain reaction. Specific kinase activities of CDK 2 and CDK 4 were evaluated using fluorescent peptide biosensors. Results CDK 2–cyclin E expression and activity were significantly increased in psoriatic epidermis compared with uninvolved adjacent skin. In contrast, CDK 4–cyclin D1 activity was inhibited, although its expression was increased in psoriatic epidermis and its transcription slightly inhibited. p27 expression was reduced, while p16 and p21 expression was induced in psoriatic epidermis. Conclusions Epidermal CDK 2 activity is increased in psoriatic epidermis while CDK 4 activity is completely inhibited. These alterations are not associated with changes in CDK transcription and instead involve post‐translational control mediated by decreased expression of p27 and p16 overexpression, respectively.What's already known about this topic?Cyclin‐dependent kinases (CDKs) are involved in cell‐cycle progression. The levels of cyclin partners and CDK inhibitors regulate their activity. Psoriasis is a chronic T‐cell‐driven inflammatory skin disease characterized by hyperproliferation of basal epidermal cells.What does this study add?Thanks to fluorescent peptide biosensors, this study demonstrates that epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations involve post‐translational control mediated by decreased expression of p27, and p16 overexpression, respectively.What is the translational message?CDK2 and CDK4 are involved in regulation of cell‐cycle progression, and psoriasis is characterized by hyperproliferation of basal epidermal cells. Epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations are not associated with changes in CDK transcription and instead involve post‐translational control mediated by decreased expression of p27 and p16 overexpression, respectively. Pharmacological modulation of CDK2 and CDK4 may constitute a promising therapeutic strategy.