MOLECULAR CHARACTERIZATION OF THE POST-TRANSLATIONAL REGULATORY MECHANISM OF MOAP-1

Abstract

Bcl-2 protein family regulates the commitment of cells to apoptosis. By regulating the activation of Bax and Bak, these proteins control the release of apoptogenic factors from mitochondria. MOAP-1 was cloned as a Bax-associating protein. In healthy cells, MOAP-1 is a short-lived protein, which is constitutively degraded. Apoptotic stimuli stabilize MOAP-1 and induce its association with Bax. Higher levels of MOAP-1 sensitize cancer cells to chemotherapeutic drugs, suggesting mechanisms that are involved in regulating its protein stability can be valuable targets for cancer treatment. Understanding of the post-translational modifications of MOAP-1 is vital. In this study, we examined ubiquitination and phosphorylation as prospective regulatory mechanisms of MOAP-1. We identified TRIM11 as a putative E3 ubiquitin ligase of MOAP-1 and revealed that protein stability of MOAP-1 is regulated by phosphorylation at serines 27, 29 and 31 and demonstrated the involvement of the ERK/MAPK signaling in regulation of MOAP-1.