PMID- 27320013 OWN - NLM STAT- MEDLINE DCOM- 20170601 LR - 20231213 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1861 IP - 9 Pt A DP - 2016 Sep TI - Low-density lipoprotein upregulate SR-BI through Sp1 Ser702 phosphorylation in hepatic cells. PG - 1066-1075 LID - S1388-1981(16)30153-6 [pii] LID - 10.1016/j.bbalip.2016.06.001 [doi] AB - Scavenger receptor class B type I (SR-BI) is one of the key proteins in the process of reverse cholesterol transport (RCT), and its major function is to uptake high density lipoprotein (HDL) cholesterol from plasma into liver cells. The regulation of SR-BI expression is important for controlling serum lipid content and reducing the risks of cardiovascular diseases. Here we found that SR-BI expression was significantly increased by LDL in vivo and in vitro, and the transcription factor specific protein 1 (Sp1) plays a critical role in this process. Results from co-immunoprecipitation experiments indicate that the activation of SR-BI was associated with Sp1-recruited protein complexes in the promoter region of SR-BI, where histone acetyltransferase p300 was recruited and histone deacetylase HDAC1 was dismissed. As a result, histone acetylation increased, leading to activation of SR-BI transcription. With further investigation, we found that LDL phosphorylated Sp1 through ERK1/2 pathway, which affected Sp1 protein complexes formation in SR-BI promoter. Using mass spectrometry and site directed mutagenesis, a new Sp1 phosphorylation site Ser702 was defined to be associated with Sp1-HDAC1 interaction and may be important in SR-BI activation, shedding light on the knowledge of delicate mechanism of hepatic HDL receptor SR-BI gene modulation by LDL. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Yang, Fan AU - Yang F AD - Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China. FAU - Du, Yu AU - Du Y AD - Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China. FAU - Zhang, Jin AU - Zhang J AD - Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China. FAU - Jiang, Zhibo AU - Jiang Z AD - Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China. FAU - Wang, Li AU - Wang L AD - Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China. Electronic address: capricornkey@163.com. FAU - Hong, Bin AU - Hong B AD - Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China. Electronic address: binhong69@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160615 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Apolipoproteins E) RN - 0 (Cholesterol, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (SCARB1 protein, human) RN - 0 (Scavenger Receptors, Class B) RN - 0 (Sp1 Transcription Factor) RN - 0 (SP1 protein, human) RN - EC 2.3.1.48 (p300-CBP Transcription Factors) RN - EC 2.3.1.48 (p300-CBP-associated factor) RN - EC 3.5.1.98 (HDAC1 protein, human) RN - EC 3.5.1.98 (Histone Deacetylase 1) SB - IM MH - Animals MH - Apolipoproteins E/*genetics MH - Cholesterol, HDL/genetics/metabolism MH - Gene Expression Regulation/genetics MH - Hep G2 Cells MH - Hepatocytes MH - Histone Deacetylase 1/*genetics/metabolism MH - Humans MH - Lipoproteins, LDL/genetics/metabolism MH - Liver/metabolism MH - Mice MH - Mice, Knockout MH - Phosphorylation MH - Promoter Regions, Genetic MH - Protein Binding MH - Scavenger Receptors, Class B/*genetics/metabolism MH - Sp1 Transcription Factor/*biosynthesis/genetics MH - Transcriptional Activation/genetics MH - p300-CBP Transcription Factors/genetics/*metabolism OTO - NOTNLM OT - Atherosclerosis OT - Histone acetyltransferase/deacetylase OT - Low density lipoprotein (LDL) OT - Scavenger receptor class B type I (SR-BI) OT - Specific protein 1 (Sp1) OT - Transcriptional regulation EDAT- 2016/06/21 06:00 MHDA- 2017/06/02 06:00 CRDT- 2016/06/21 06:00 PHST- 2016/01/15 00:00 [received] PHST- 2016/05/04 00:00 [revised] PHST- 2016/06/10 00:00 [accepted] PHST- 2016/06/21 06:00 [entrez] PHST- 2016/06/21 06:00 [pubmed] PHST- 2017/06/02 06:00 [medline] AID - S1388-1981(16)30153-6 [pii] AID - 10.1016/j.bbalip.2016.06.001 [doi] PST - ppublish SO - Biochim Biophys Acta. 2016 Sep;1861(9 Pt A):1066-1075. doi: 10.1016/j.bbalip.2016.06.001. Epub 2016 Jun 15.