B-cell Translocation Gene 2: Expression in the Rat Ovary and Potential Association With Adenine Nucleotide Translocase 2 in Mitochondria

Mol Cell Endocrinol. 2013 Mar 10;367(1-2):31-40. doi: 10.1016/j.mce.2012.12.013. Epub 2012 Dec 23.

Abstract

The B-cell translocation gene 2 (Btg2) is an anti-proliferative tumor suppressor gene that behaves as a transcriptional regulator. The present study investigated gonadotropin induction of Btg2 in the rat ovary and the mechanism of Btg2 action as a partner of mitochondrial protein adenine nucleotide translocase 2 (Ant2). Transient induction of Btg2 as well as Btg1 mRNA levels by LH/hCG was observed in ovarian granulosa cells. Btg2 protein levels were also stimulated by LH/hCG. LH-induced gene expression of Btg2 required ERK signal pathway. Studies of deletion mutants in HeLa cells showed that deletion of Btg2 C-terminus (Btg2/ΔC) abolished the interaction with Ant2. In fact, the expression levels of Btg2/ΔC construct were decreased in mitochondrial fraction. Btg2 was also expressed in mitochondria and interacted with Ant2 in preovulatory granulosa cells. Interestingly, a Btg2/ΔC construct inhibited an action of Btg2 wild-type on ATP and H(2)O(2) production. These findings demonstrate the gonadotropin stimulation of Btg2 in the ovary and, the physical interaction of Btg2 with Ant2 in mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotide Translocator 2 / genetics
  • Adenine Nucleotide Translocator 2 / metabolism*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Chorionic Gonadotropin / pharmacology
  • Female
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • HeLa Cells
  • Humans
  • Hydrogen Peroxide / metabolism
  • Immediate-Early Proteins / chemistry
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Luteinizing Hormone / pharmacology
  • Mitochondria / drug effects
  • Mitochondria / enzymology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Ovary / drug effects
  • Ovary / metabolism*
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sheep
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Adenine Nucleotide Translocator 2
  • BTG2 protein, rat
  • Btg1 protein, rat
  • Chorionic Gonadotropin
  • Immediate-Early Proteins
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • Adenosine Triphosphate
  • Luteinizing Hormone
  • Hydrogen Peroxide