STAT1 is a member of the STAT family of transcription factors. STAT1 is involved in upregulating genes due to a signal by interferons []. STAT1 forms a heterodimer with STAT2 that can bind Interferon Stimulated Response Element (ISRE) promoter element in response to either IFN-alpha or IFN-beta stimulation [].STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins []. Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes []. STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 [].
This region is found in the mammalian signal transducer and activation of transcription (STAT) 2 protein, and is approximately 60 amino acids in length. The family is found in association with , , , . There is a conserved DLP sequence motif. STATs are involved in transcriptional regulation and are the only regulators known to be modulated by tyrosine phosphorylation. STAT2 forms a trimeric complex with STAT1 and IRF-9 (Interferon Regulatory Factor 9), on activation of the cell by interferon, which is called ISGF3 (Interferon-stimulated gene factor 3). The C-terminal domain of STAT2 contains a nuclear export signal (NES) which allows export of STAT2 into the cytoplasm along with any complexed molecules.
SETD2 is a histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate [, ]. It is required for DNA double-strand break repair and activation of the p53-mediated checkpoint []. SETD2-inactivation has been linked to tumour development []. SETD2 also methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy []. Moreover, SETD2 is also involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription [].
STAT2 is a member of the STAT protein family. In response to interferon, STAT2 forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly []. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with STAT2, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus []. This entry represents the SH2 domain of STAT2.STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins []. Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes []. STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 [].
This entry represents the SET domain found in SETD2 from animals, ASHH2 from plants and Set2 from fungi. Proteins containing this domain are a group of histone methyltransferases that methylates histone H3 to form H3K36me [, ].Yeast Set2 is involved in transcription elongation as well as in transcription repression []. The methyltransferase activity of budding yeast Set2 requires the recruitment to the RNA polymerase II, which is CTK1 dependent [, , , , , , ]. Plant ASHH2 is required for the correct expression of genes essential to reproductive development [].SETD2 acts as histone-lysine N-methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using demethylated 'Lys-36' (H3K36me2) as substrate [, ]. SETD2 is also required for DNA double-strand break repair and activation of the p53-mediated checkpoint []. SETD2-inactivation has been linked to tumour development []. SETD2 also methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy []. Moreover, SETD2 is also involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription [].SETD2 has been linked to several human diseases, including Renal cell carcinoma (RCC) [], Luscan-Lumish syndrome (LLS) [], Leukemia, acute lymphoblastic (ALL) []and Leukemia, acute myelogenous (AML) [, ].
