PMID- 20006573 OWN - NLM STAT- MEDLINE DCOM- 20100308 LR - 20171116 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 391 IP - 2 DP - 2010 Jan 8 TI - Tumor Necrosis Factor alpha (TNFalpha) regulates CD40 expression through SMAR1 phosphorylation. PG - 1255-61 LID - 10.1016/j.bbrc.2009.12.055 [doi] AB - CD40 plays an important role in mediating inflammatory response and is mainly induced by JAK/STAT phosphorylation cascade. TNFalpha is the key cytokine that activates CD40 during inflammation and tumorigenesis. We have earlier shown that SMAR1 can repress the transcription of Cyclin D1 promoter by forming a HDAC1 dependent repressor complex. In this study, we show that SMAR1 regulates the transcription of NF-kappaB target gene CD40. SMAR1 recruits HDAC1 and forms a repressor complex on CD40 promoter and keeps its basal transcription in check. Further, we show that TNFalpha stimulation induces SMAR1 phosphorylation at Ser-347 and promotes its cytoplasmic translocation, thus releasing its negative effect. Concomitantly, TNFalpha induced phosphorylation of STAT1 at Tyr-701 by JAK1 facilitates its nuclear translocation and activation of CD40 through p300 recruitment and core Histone-3 acetylation. Thus, TNFalpha mediated regulation of CD40 expression occurs by dual phosphorylation of SMAR1 and STAT1. CI - Copyright 2009 Elsevier Inc. All rights reserved. FAU - Singh, Kamini AU - Singh K AD - National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411 007, Maharashtra, India. FAU - Sinha, Surajit AU - Sinha S FAU - Malonia, Sunil Kumar AU - Malonia SK FAU - Chattopadhyay, Samit AU - Chattopadhyay S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091216 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Banp protein, mouse) RN - 0 (CD40 Antigens) RN - 0 (Cell Cycle Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Nuclear Proteins) RN - 0 (STAT1 Transcription Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - 452VLY9402 (Serine) RN - EC 2.7.10.2 (Janus Kinases) SB - IM MH - Animals MH - CD40 Antigens/*genetics MH - Cell Cycle Proteins/*metabolism MH - Cell Line MH - Cytoplasm/metabolism MH - DNA-Binding Proteins/*metabolism MH - *Gene Expression Regulation MH - Janus Kinases/metabolism MH - Mice MH - Nuclear Proteins/*metabolism MH - Phosphorylation MH - Promoter Regions, Genetic MH - Protein Transport MH - STAT1 Transcription Factor/metabolism MH - Serine/metabolism MH - Tumor Necrosis Factor-alpha/*metabolism/pharmacology EDAT- 2009/12/17 06:00 MHDA- 2010/03/10 06:00 CRDT- 2009/12/17 06:00 PHST- 2009/11/19 00:00 [received] PHST- 2009/12/10 00:00 [accepted] PHST- 2009/12/17 06:00 [entrez] PHST- 2009/12/17 06:00 [pubmed] PHST- 2010/03/10 06:00 [medline] AID - S0006-291X(09)02428-0 [pii] AID - 10.1016/j.bbrc.2009.12.055 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2010 Jan 8;391(2):1255-61. doi: 10.1016/j.bbrc.2009.12.055. Epub 2009 Dec 16.