Hepatocellular carcinoma-associated gene 2 interacts with MAD2L2

HCCA2 (hepatocellular carcinoma-associated gene 2) was initially identified as a HCC (hepatocellular carcinoma)-specific protein and subsequently, a long splice variant of HCCA2 was identified as a co-activator of transcription factor YY1 (Yin Yang 1). To investigate the role of HCCA2 in HCC genesis and progression, we screened a human fetal liver cDNA library and identified a novel HCCA2-interacting protein, MAD2L2 (MAD2 mitotic arrest deficient-like 2 (yeast)). The interaction between HCCA2 and MAD2L2 was confirmed by in vitro and in vivo binding assays and the interaction domain was mapped to the N-terminus of HCCA2 by sequential deletion. HCCA2 and MAD2L2 also colocalized in the nucleus of Hela cells. Furthermore, overexpression of HCCA2 led to cell cycle arrest at G0/G1 phase and therefore inhibited cell proliferation. Our research suggests that HCCA2 may play a novel role in cell cycle regulation.