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

BMC Cell Biol. 2007 Nov 28;8:50. doi: 10.1186/1471-2121-8-50.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects*
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Gene Expression / drug effects
  • Gene Expression / radiation effects
  • Membrane Proteins / metabolism*
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Membranes / radiation effects*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism*
  • Molecular Sequence Data
  • Mutant Proteins / metabolism
  • Protein Structure, Tertiary
  • Protein Transport / drug effects
  • Protein Transport / radiation effects
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Sequence Alignment
  • Sequence Homology
  • Staurosporine / pharmacology
  • Ultraviolet Rays*

Substances

  • LETMD1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Mutant Proteins
  • Proto-Oncogene Proteins
  • Staurosporine