STAT protein

The Signal Transducers and Activator of Transcription (STAT) protein regulates many aspects of cell growth, survival and differentiation. The transcription factorsof this family are activated by the Janus Kinase JAKand dysregulation of this pathway is frequently observed in primary tumors and leads to increased angiogenesisand enhanced survival of tumors. Knockoutstudies have provided evidence that STAT proteins are involved in the development and function of the immune systemand play a role in maintaining immune toleranceand tumor surveillance.

Types

The seven mammalian STAT family members identified are: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. STAT1 homodimers are involved in type II interferon signalling, and binds to the GAS (Interferon-Gamma Activated Sequence) promoter to induce expression of ISG (Interferon Stimulated Genes). In type I interferon signalling, STAT1-STAT2 heterodimer combines with IRF9 (Interferon Response Factor) to form ISGF3 (Interferon Stimulated Gene Factor), which binds to the ISRE (Interferon Stimulated Response Element) promoter to induce ISG expression.

Function

STAT proteins were originally described as latent cytoplasmictranscription factors that require phosphorylationfor nuclear retention. The unphosphorylated STAT proteins shuttles between cytosol and the nucleus waiting for its activation signal. Once the activated transcription factors reaches the nucleus it binds to consensus DNA-recognition motif called gamma activated sites (GAS) in the promoterregion of cytokine inducible genesand activates transcription of these genes.

Activation

Extracellular binding of cytokinesinduces activation of the intracellular Janus kinase that phosphorylates a specific tyrosine residue in the STAT protein which promotes the dimerizationof STAT monomers via their SH2 domain. The phosphorylated dimer is then actively transported in the nucleus via importin a/band RanGDP complex. Once inside the nucleus the active STAT dimer binds to cytokine inducible promoter regions of genes containing gamma activated site (GAS) motif and activate transcriptionof these genes. The STAT protein can be dephosphorylated by nuclear phosphatasesswhich leads to inactivation of STAT and the transcription factor becomes transported out of the nucleus by exportincrm1/RanGTP.

See also

• DNA-binding protein

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/STAT+protein Wikipedia article STAT protein.