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


CONCLUSIONS
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.
Cho
Goang-Won
GW
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea. goangwon@hotmail.com
Shin
Seung Min
SM
Kim
Hyun Kee
HK
Ha
Seon-Ah
SA
Kim
Sanghee
S
Yoon
Joo-Hee
JH
Hur
Soo Young
SY
Kim
Tae Eung
TE
Kim
Jin Woo
JW
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D008565:Membrane Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017385:Sequence Homology; D019311:Staurosporine / Q000494:pharmacology; D014466:Ultraviolet Rays
C476732:LETMD1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D050505:Mutant Proteins; D011518:Proto-Oncogene Proteins; D019311:Staurosporine