A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain.

Abstract

Statl and Stat3 are two members of the ligand-activated transcription factor family that serve the dual functions of signal transducers and activators of transcription. Whereas the two proteins select very similar (not identical) optimum binding sites from random oligonucleotides, differences in their binding affinity were readily apparent with natural STAT-binding sites. To take advantage of these different affinities, chimeric Statl:Stat3 molecules were used to locate the amino acids that could discriminate a general binding site from a specific binding site. The amino acids between residues -400 and -500 of these -750-amino-acid-long proteins determine the DNA-binding site specificity. Mutations within this region result in Stat proteins that are activated normally by tyrosine phosphorylation and that dimerize but have greatly reduced DNA-binding affinities.

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

“…However, preferences of Stat1, Stat3, Stat4, and Stat6 binding as dimers have been analysed. Whereas Stat5a and Stat5b dimers both preferred a TTC(T/C)N(G/A)GAA sequences, Stat1, Stat3, and Stat4 were reported to prefer somewhat more stringent TTCC(C/G)GGAA motifs (Horvath et al, 1995;Xu et al, 1996) while Stat6 prefers a TTCNTNGGAA motif .…”

NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer

“…Structurally, each of the STAT proteins has several conserved domains which are critical for its functions. DNA binding domain is observed in the central region of each STAT protein (except STAT2) and regulates DNA binding specifi city (Horvath et al, 1995). There is a conserved SH2 domain in the region between 600 and 700 amino acid residues of all seven members.…”

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

“…All STAT members contain in their structure a SH2 domain which allows their selective recruitment to the receptor-kinase activated complex and the dimerization of the STATs (Heim et al, 1995;Shuai et al, 1994;Stahl et al, 1995). Functional domains involved in DNA binding and activation of transcription have been de®ned (Horvath et al, 1995;Schindler et al, 1995;Moriggl et al, 1996Moriggl et al, , 1997Schaefer et al, 1997).…”