Lithocholic Acid Hydroxyamide Destabilizes Cyclin D1 and Induces G0/G1 Arrest by Inhibiting Deubiquitinase USP2a.
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ABSTRACT:
SUBMITTER: Magiera K
PROVIDER: S-EPMC5404848 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Lithocholic Acid Hydroxyamide Destabilizes Cyclin D1 and Induces G<sub>0</sub>/G<sub>1</sub> Arrest by Inhibiting Deubiquitinase USP2a.
Magiera Katarzyna K Tomala Marcin M Kubica Katarzyna K De Cesare Virginia V Trost Matthias M Zieba Bartosz J BJ Kachamakova-Trojanowska Neli N Les Marcin M Dubin Grzegorz G Holak Tad A TA Skalniak Lukasz L
Cell chemical biology 20170323 4
USP2a is a deubiquitinase responsible for stabilization of cyclin D1, a crucial regulator of cell-cycle progression and a proto-oncoprotein overexpressed in numerous cancer types. Here we report that lithocholic acid (LCA) derivatives are inhibitors of USP proteins, including USP2a. The most potent LCA derivative, LCA hydroxyamide (LCAHA), inhibits USP2a, leading to a significant Akt/GSK3β-independent destabilization of cyclin D1, but does not change the expression of p27. This leads to the defe ...[more]
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