期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 27, 期 18, 页码 6300-6308出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00613-07
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资金
- NCI NIH HHS [T32 CA09673, T32 CA009673] Funding Source: Medline
- NIAID NIH HHS [AI34420, AI32489, R01 AI032489, R37 AI034420] Funding Source: Medline
- NIGMS NIH HHS [F32 GM068566, GM068566] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [T32CA009673] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI034420, R37AI034420, R01AI032489] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [F32GM068566] Funding Source: NIH RePORTER
Cooperation between STAT3 and c-Jun in driving transcription during transfection of reporter constructs is well established, and both proteins are present on some interleukin-6 (IL-6) STAT3-dependent promoters on chromosomal loci. We report that small interfering RNA knockdown of c-Jun or c-Fos diminishes IL-6 induction of some but not all STAT3-dependent mRNAs. Specific contact sites in STAT3 responsible for interaction of a domain of STAT3 with c-Jun were known. Here we show that the B-zip domain of c-Jun interacts with STAT3 and that c-Jun mutation R261A or R261D near but not in the DNA binding domain blocks in vitro STAT3-c-Jun interaction and decreases costimulation of transcription in transfection assays. Cooperative binding to DNA of tyrosine-phosphorylated STAT3 and both wild-type and R261A mutant c-Jun was observed. Even c-Jun mutant R261D, which on its own did not bind DNA, bound DNA weakly in the presence of STAT3. We conclude that a functional interaction between STAT3 and c-Jun while bound to chromosomal DNA elements exists and is necessary for driving transcription on at least some STAT3 target genes. Identifying such required interactive protein interfaces should be a stimulus to search for compounds that could ultimately inhibit the activity of STAT3 in tumors dependent on persistently active STAT3.
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