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Inhibitory role of RhoA on senescence‐like growth arrest by a mechanism involving modulation of phosphatase activity
Author(s) -
Park Chaehwa,
Lee Inkyoung,
Jang Jun Ho,
Kang Won Ki
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.07.007
Subject(s) - rhoa , phosphatase , senescence , dephosphorylation , microbiology and biotechnology , mapk/erk pathway , carcinogenesis , protein phosphatase 2 , phosphorylation , chemistry , biology , signal transduction , cancer , genetics
Recently, negative effects of phosphatase in tumorigenesis and metastasis have been suggested in various tumor types. In this study, we showed that RhoA activation modulated phosphatase during senescence‐like arrest in human prostate cancer cells. Under senescence‐inducing condition, decreased Erk phosphorylation was detected in caRhoA‐transfected cells and inactivation of Erk, but not p38, prevented doxorubicin‐induced cell senescence. Cells were induced to senescence by inhibition of phosphatase activity (VHR, MKP3, or PP2A) without additional cellular stress. Of interest, caRhoA prevented doxorubicin‐induced decrease of phosphatase. Thus, we postulate that RhoA signaling may protect cells against cellular senescence by maintaining phosphatase activity and Erk dephosphorylation.