The formin DAAM1 regulates the deubiquitinase activity of USP10 and integrin homeostasis.

ABSTRACT: The differentiation of fibroblasts into pathological myofibroblasts during wound healing is characterized by increased cell surface expression of αv-integrins. Our previous studies found that the deubiquitinase (DUB) USP10 removes ubiquitin from αv-integrins, leading to cell surface integrin accumulation, subsequent TGFβ1 activation, and pathological myofibroblast differentiation. In this study, a yeast two-hybrid screen revealed a novel binding partner for USP10, the formin, DAAM1. We found that DAAM1 binds to and inhibits USP10's DUB activity through the FH2 domain of DAAM1 independent of its actin functions. The USP10/DAAM1 interaction was also supported by proximity ligation assay (PLA) in primary human corneal fibroblasts. Treatment with TGFβ1 significantly increased USP10 and DAAM1 p

SUBMITTER: Phillips AT 

PROVIDER: S-EPMC10839120 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature