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

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.
Mesh Terms:
14-3-3 Proteins, Animals, Apoptosis, Carrier Proteins, Cell Line, DNA Fragmentation, Flow Cytometry, Humans, In Situ Hybridization, Mice, Protein Binding, Protein Isoforms, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-raf, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Tissue Distribution, Two-Hybrid System Techniques, Tyrosine 3-Monooxygenase, bcl-Associated Death Protein
Exp. Cell Res.
Date: Nov. 15, 2001
Download Curated Data For This Publication
137634
Switch View:
  • Interactions 18