Functional conservation of 14-3-3 isoforms in inhibiting bad-induced apoptosis

Exp Cell Res. 2001 Nov 15;271(1):142-51. doi: 10.1006/excr.2001.5376.

Abstract

14-3-3 proteins are a family of homologous eukaryotic molecules with seven distinct isoforms in mammalian cells. Isoforms of 14-3-3 proteins interact with diverse ligands and are involved in the regulation of mitogenesis, cell cycle progression, and apoptosis. However, whether different 14-3-3 isoforms are responsible for distinct functions remains elusive. Here we report that multiple isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl. In a functional assay of 14-3-3 isoforms, all mammalian 14-3-3 isoforms could inhibit Bad-induced apoptosis. Thus, 14-3-3 function in regulating one of its ligands, Bad, is conserved among mammalian isoforms. We addressed whether 14-3-3 isoforms are differentially expressed in tissues, which may in part determine isoform-specific interactions. In situ hybridization revealed that 14-3-3zeta was present in most tissues tested, but sigma was preferentially expressed in epithelial cells. Thus, isoforms of 14-3-3 can interact and control the function of selected protein ligands, and differential tissue distribution of 14-3-3 isoforms may contribute to their specific interactions and subsequent downstream signaling events.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Animals
  • Apoptosis / physiology*
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA Fragmentation
  • Flow Cytometry
  • Humans
  • In Situ Hybridization
  • Mice
  • Protein Binding
  • Protein Isoforms / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Tissue Distribution
  • Two-Hybrid System Techniques
  • Tyrosine 3-Monooxygenase / chemistry
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism*
  • bcl-Associated Death Protein

Substances

  • 14-3-3 Proteins
  • BAD protein, human
  • Bad protein, mouse
  • Carrier Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • bcl-Associated Death Protein
  • Tyrosine 3-Monooxygenase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf