Fank1 interacts with Jab1 and regulates cell apoptosis via the AP-1 pathway

Cell Mol Life Sci. 2011 Jun;68(12):2129-39. doi: 10.1007/s00018-010-0559-4. Epub 2010 Oct 27.

Abstract

Regulation of apoptosis at various stages of differentiation plays an important role in spermatogenesis. Therefore, the identification and characterisation of highly expressed genes in the testis that are involved in apoptosis is of great value to delineate the mechanism of spermatogenesis. Here, we reported that Fank1, a novel gene highly expressed in testis, functioned as an anti-apoptotic protein that activated the activator protein 1 (AP-1) pathway. We found that Jab1 (Jun activation domain-binding protein 1), a co-activator of AP-1, specifically interacted with Fank1. Reporter analyses showed that Fank1 activated AP-1 pathway in a Jab1-dependent manner. Fank1 overexpression also increased the expression and activation of endogenous c-Jun. Further study showed that Fank1 inhibited cell apoptosis by upregulating and activating endogenous c-Jun and its downstream target, Bcl-3. This process was shown to be Jab1 dependent. Taken together, our results indicated that by interacting with Jab1, Fank1 could suppress cell apoptosis by activating the AP-1-induced anti-apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • B-Cell Lymphoma 3 Protein
  • COP9 Signalosome Complex
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Peptide Hydrolases / metabolism*
  • Peptide Hydrolases / physiology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Signal Transduction*
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology
  • Transfection

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • DNA-Binding Proteins
  • Fank1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Transcription Factors
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex