The highly conserved ubiquitous 14-3-3 family of proteins is expressed in diverse
eukaryotic organisms. They are capable of binding to a variety of protooncogenes
and key enzymes important in different intracellular signaling pathways including
mitogen-activated cell cycle progression, signal transduction mediated by protein
kinase C isoforms, and oncogenesis Aitkin et al 1992 .
NCBI Summary:
This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the rat ortholog. It is induced by growth factors in human vascular smooth muscle cells, and is also highly expressed in skeletal and heart muscles, suggesting an important role for this protein in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. [provided by RefSeq]
Proteins of the 14-3-3 family bind diverse enzymes and signaling molecules,
including Raf-1 kinase, B-Raf, phosphatidyl inositol 3 kinase, CDC25 phosphatases,
Bcr, Cbl, and polyoma middle T antigen. They are important in intracellular
signaling, cell cycle control, oncogenesis, and neurotransmitter biosynthesis in
neuron.Papin et al 1996 .
Cellular localization
Cytoplasmic
Comment
Ovarian function
Follicle atresia
Comment
Hsu et al 1997 reported the interference of BAD (Bcl-xL/Bcl-2-associated death
promoter)-induced apoptosis in mammalian cells by 14-3-3
isoforms. They hypothesized that BAD, in addition to binding Bcl-xL and Bcl-2, may interact
with proteins outside the Bcl-2 family. Using the yeast two-hybrid system to
search for BAD-binding proteins in an ovarian fusion cDNA library, they
identified multiple cDNA clones encoding different isoforms of 14-3-3, a group of
evolutionally conserved proteins essential for signal transduction and cell cycle
progression. Point mutation of BAD in one (S137A), but not the other (S113A),
putative binding site found in diverse 14-3-3 interacting proteins abolished the
interaction between BAD and 14-3-3 without affecting interactions between BAD
and Bcl-2.
14-3-3 proteins are constitutively expressed in all cells.
Expression of 14-3-3 protein isoforms in mouse oocytes, eggs and ovarian follicular development. De S et al. ABSTRACT: BACKGROUND: The 14-3-3 (YWHA) proteins are a highly conserved, ubiquitously expressed family of proteins. Seven mammalian isoforms of 14-3-3 are known (beta, gamma, epsilon, zeta, eta, tau and sigma). These proteins associate with many intracellular proteins involved in a variety of cellular processes including regulation of the cell cycle, metabolism and protein trafficking. We are particularly interested in the role of 14-3-3 in meiosis in mammalian eggs and the role 14-3-3 proteins may play in ovarian function. Therefore, we examined the expression of 14-3-3 proteins in mouse oocyte and egg extracts by Western blotting after polyacrylamide gel electrophoresis, viewed fixed cells by indirect immunofluorescence, and examined mouse ovarian cells by immunohistochemical staining to study the expression of the different 14-3-3 isoforms. RESULTS: We have determined that all of the mammalian 14-3-3 isoforms are expressed in mouse eggs and ovarian follicular cells including oocytes. Immunofluorescence confocal microscopy of isolated oocytes and eggs confirmed the presence of all of the isoforms with characteristic differences in some of their intracellular localizations. For example, some isoforms (beta, epsilon, gamma, and zeta) are expressed more prominently in peripheral cytoplasm compared to the germinal vesicles in oocytes, but are uniformly dispersed within eggs. On the other hand, 14-3-3eta is diffusely dispersed in the oocyte, but attains a uniform punctate distribution in the egg with marked accumulation in the region of the meiotic spindle apparatus. Immunohistochemical staining detected all isoforms within ovarian follicles, with some similarities as well as notable differences in relative amounts, localizations and patterns of expression in multiple cell types at various stages of follicular development. CONCLUSIONS: We found that mouse oocytes, eggs and follicular cells within the ovary express all seven isoforms of the 14-3-3 protein. Examination of the differential expression of these 14-3-3 isoforms in female germ cells and ovarian follicles provides the foundation for further investigating 14-3-3 isoform-specific interactions with key proteins involved in ovarian development, meiosis and oocyte maturation. This will lead to a better understanding of the individual functional roles of the 14-3-3 protein isoforms in mammalian oogenesis and female reproductive development.
Follicle stages
Primordial, Primary, Secondary, Antral, Preovulatory, Corpus luteum