Phosphorylation of cell cycle and apoptosis regulatory protein-1 by stress activated protein kinase P38γ is a novel mechanism of apoptosis signaling by genotoxic chemotherapy.

ABSTRACT: CARP-1, a perinuclear phospho-protein, regulates cell survival and apoptosis signaling induced by genotoxic drugs. However, kinase(s) phosphorylating CARP-1 and down-stream signal transduction events remain unclear. Here we find that CARP-1 Serine (S)⁶²⁶ and Threonine (T)⁶²⁷ substitution to Alanines (AA) inhibits genotoxic drug-induced apoptosis. CARP-1 T⁶²⁷ is followed by a Proline (P), and this TP motif is conserved in vertebrates. Based on these findings, we generated affinity-purified, anti-phospho-CARP-1 T⁶²⁷ rabbit polyclonal antibodies, and utilized them to elucidate chemotherapy-activated, CARP-1-dependent cell growth signaling mechanisms. Our kinase profiling studies revealed that MAPKs/SAPKs phosphorylated CARP-1 T⁶²⁷. We the

SUBMITTER: Venkatesh J 

PROVIDER: S-EPMC11096501 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature