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STAT protein



  The Signal Transducers and Activator of Transcription (STAT, also, called signal transduction and transcription) proteins regulate many aspects of cell growth, survival and differentiation. The transcription factors of this family are activated by the Janus Kinase JAK and dysregulation of this pathway is frequently observed in primary tumors and leads to increased angiogenesis, enhanced survival of tumors and immunosuppression. Knockout studies have provided evidence that STAT proteins are involved in the development and function of the immune system and play a role in maintaining immune tolerance and tumor surveillance.

STAT protein, all-alpha domain
Identifiers
Symbol STAT_alpha
Pfam PF01017
InterPro IPR013800
SCOP 1bgf
OPM protein 1bg1
Available PDB structures:

1yvlA:136-315 1bf5A:136-315 1bg1A:138-319 1y1uA:138-330

STAT protein, DNA binding domain
Identifiers
Symbol STAT_bind
Pfam PF02864
InterPro IPR013801
SCOP 1bgf
OPM protein 1bg1
Available PDB structures:

1yvlA:317-567 1bf5A:317-567 1bg1A:321-574 1y1uA:332-583

STAT protein, protein interaction domain
Identifiers
Symbol STAT_int
Pfam PF02865
InterPro IPR013799
SCOP 1bgf
Available PDB structures:

1yvlA:2-122 1bgfA:2-122

Additional recommended knowledge

Contents

STAT family

The first two STAT proteins were identified in the interferon system

The seven mammalian STAT family members identified are: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and 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 signaling, 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 cytoplasmic transcription factors that require phosphorylation for 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 promoter region of cytokine inducible genes and activates transcription of these genes.

Activation

Extracellular binding of cytokines induces activation of the intracellular Janus kinase that phosphorylates a specific tyrosine residue in the STAT protein which promotes the dimerization of STAT monomers via their SH2 domain. The phosphorylated dimer is then actively transported in the nucleus via importin a/b and 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 transcription of these genes. The STAT protein can be dephosphorylated by nuclear phosphatases which leads to inactivation of STAT and the transcription factor becomes transported out of the nucleus by exportin crm1/RanGTP.

See also

References

    Additional images

     
    This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "STAT_protein". A list of authors is available in Wikipedia.
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