Research article

HCCR-1, a novel oncogene, encodes a mitochondrial outer membrane protein and suppresses the UVC-induced apoptosis

Goang-Won Cho¹ , Seung Min Shin¹ , Hyun Kee Kim¹ , Seon-Ah Ha¹ , Sanghee Kim¹ , Joo-Hee Yoon² , Soo Young Hur² , Tae Eung Kim² and Jin Woo Kim^1,2

¹Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea

²Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea

author email corresponding author email

BMC Cell Biology 2007, 8:50doi:10.1186/1471-2121-8-50

Published:	28 November 2007

Abstract

Background

The Human cervical cancer oncogene (HCCR-1) has been isolated as a human oncoprotein, and has shown strong tumorigenic features. Its potential role in tumorigenesis may result from a negative regulation of the p53 tumor suppressor gene.

Results

To investigate the biological function of HCCR-1 in the cell, we predicted biological features using bioinformatic tools, and have identified a LETM1 homologous domain at position 75 to 346 of HCCR-1. This domain contains proteins identified from diverse species predicted to be mitochondrial proteins. Fluorescence microscopy and fractionation experiments showed that HCCR-1 is located in mitochondria in the COS-7, MCF-7 and HEK/293 cell lines, and subcompartamentally at the outer membrane in the HEK/293 cell line. The topological structure was revealed as the NH₂-terminus of HCCR-1 oriented toward the cytoplasm. We also observed that the D1-2 region, at position 1 to 110 of HCCR-1, was required and sufficient for posttranslational mitochondrial import. The function of HCCR-1 on mitochondrial membrane is to retard the intrinsic apoptosis induced by UVC and staurosporine, respectively.

Conclusion

Our experiments show the biological features of HCCR-1 in the cell, and suggest that uncontrolled expression of HCCR-1 may cause mitochondrial dysfunction that can result in resisting the UVC or staurosporine-induced apoptosis and progressing in the tumor formation.