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C-terminal binding protein-mediated transcriptional repression is regulated by X-linked inhibitor of apoptosis

Ji Sun Lee1, Sun Kyung Lee, Hong-Duk Youn

  • 1Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.

Biochemical and Biophysical Research Communications
|December 6, 2011
PubMed

Insights

Inhibitors of Apoptosis Proteins (IAPs) regulate apoptosis. This study reveals IAPs, specifically XIAP, target CtBP1 for degradation, impacting gene expression.

Area of Science:

  • * Molecular Biology
  • * Cell Biology
  • * Genetics

Background:

  • * Inhibitors of Apoptosis Proteins (IAPs) are critical negative regulators of apoptosis.
  • * Understanding novel functions of IAPs is essential for cellular regulation research.
  • * Diap1 and XIAP are key IAP proteins involved in apoptosis regulation.

Purpose of the Study:

  • * To identify proteins interacting with Diap1 in insect S2 cells.
  • * To investigate the functional relationship between IAPs and C-terminal binding proteins (CtBPs).
  • * To elucidate the role of XIAP in regulating CtBP1-mediated gene expression.

Main Methods:

  • * Protein-protein interaction assays using insect S2 cells.
  • * Co-immunoprecipitation to detect protein binding.
  • * Ubiquitination assays and proteasome degradation studies.
  • * Analysis of CtBP1 target gene expression in relation to XIAP levels.

Main Results:

  • * Diap1 was found to interact with Drosophila C-terminal binding protein (dCtBP).
  • * CtBP1 was identified to interact with human X-linked inhibitor of apoptosis protein (XIAP).
  • * IAPs were shown to ubiquitinate CtBPs, targeting them for proteasome degradation.
  • * XIAP expression was demonstrated to regulate the expression of CtBP1 target genes.

Conclusions:

  • * This study establishes a novel interaction between IAPs and CtBPs.
  • * XIAP specifically regulates CtBP1, influencing its transcriptional co-repression activity.
  • * XIAP's role in regulating CtBP1 levels suggests a mechanism for controlling gene expression via protein degradation.

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