MOAP-1: A Candidate Tumor Suppressor Protein
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Abstract
Modulator of apoptosis 1 (MOAP-1) is a BH3-like protein that plays a key role in death receptor-dependent apoptosis and cooperates with the tumor suppressor protein Ras association domain family 1A (RASSF1A) to promote Bax activation during cell death. Although loss of RASSF1A expression is frequently observed in human cancers, it is currently unknown if MOAP-1 expression may also be affected during carcinogenesis to result in uncontrolled malignant growth. Therefore, we sought to investigate the role of MOAP-1 in cancer development. Here, we demonstrate that MOAP-1 can effectively inhibit cell proliferation both in vitro and in vivo and undergoes frequent loss of expression during carcinogenesis. The ability of MOAP-1 to suppress tumor formation requires protein kinase C (PKC)-dependent non-degradative ubiquitination at lysine residue K278 and may involve the novel MOAP-1-interacting protein receptor for activated C-kinase 1 (RACK1). Our data indicate that MOAP-1 is a candidate tumor suppressor protein regulated by PKC-dependent ubiquitination.