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.

Pfam_box
Symbol = STAT_alpha
Name = STAT protein, all-alpha domain


width =
caption =
Pfam= PF01017
InterPro= IPR013800
SMART=
Prosite =
SCOP = 1bgf
TCDB =
OPM family=
OPM protein= 1bg1
PDB=PDB3|1yvlA:136-315 PDB3|1bf5A:136-315 PDB3|1bg1A:138-319PDB3|1y1uA:138-330

Pfam_box
Symbol = STAT_bind
Name = STAT protein, DNA binding domain


width =
caption =
Pfam= PF02864
InterPro= IPR013801
SMART=
Prosite =
SCOP = 1bgf
TCDB =
OPM family=
OPM protein= 1bg1
PDB=PDB3|1yvlA:317-567 PDB3|1bf5A:317-567 PDB3|1bg1A:321-574PDB3|1y1uA:332-583

Pfam_box
Symbol = STAT_int
Name = STAT protein, protein interaction domain


width =
caption =
Pfam= PF02865
InterPro= IPR013799
SMART=
Prosite =
SCOP = 1bgf
TCDB =
OPM family=
OPM protein=
PDB=PDB3|1yvlA:2-122 PDB3|1bgfA:2-122

TAT 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.

ee also

*JAK-STAT pathway
*DNA-binding protein

References

=Additional

External links

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