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Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter

Authors
 Bu-Nam Jeon  ;  Yeon-Sook Kim  ;  Won-Il Choi  ;  Dong-In Koh  ;  Min-Kyeong Kim  ;  Jae-Hyeon Yoon  ;  Min-Young Kim  ;  Benjamin Hur  ;  Philip Dong-Hyun Paik  ;  Man-Wook Hur 
Citation
 JOURNAL OF LIPID RESEARCH, Vol.53(4) : 755-766, 2012 
Journal Title
 JOURNAL OF LIPID RESEARCH 
ISSN
 0022-2275 
Issue Date
2012
MeSH
3T3-L1 Cells ; Animals ; Cell Dedifferentiation ; Cell Differentiation ; Cell Proliferation ; Doxycycline/pharmacology ; Electrophoretic Mobility Shift Assay ; Enzyme Activation ; Fatty Acid Synthase, Type I/genetics ; Fatty Acid Synthase, Type I/metabolism* ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; HCT116 Cells ; HEK293 Cells ; Humans ; Immunoprecipitation ; Male ; Mice ; Pregnancy ; Promoter Regions, Genetic* ; Protein Binding ; Protein Interaction Domains and Motifs ; Proteins/genetics ; Proteins/metabolism* ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Sterol Regulatory Element Binding Protein 1/genetics ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Transcriptional Activation
Keywords
kidney cancer-related POZ domain and Krüppel-like protein ; sterol responsive element binding protein-1c ; specificity protein 1 ; fatty acid synthase ; transcription ; oncoprotein ; lipid ; fatty acid
Abstract
Kr-pok (kidney cancer-related POZ domain and Krüppel-like protein) is a new proto-oncogenic POZ-domain transcription factor. Fatty acid synthase gene (FASN) encodes one of the key enzymes in fatty acids synthesis and is the only enzyme that synthesizes fatty acids in cancer cells. Sp1 and SREBP-1c are the two major transcription activators of FASN. We investigated whether Kr-pok modulates transcription of the FASN. FASN expression is significantly decreased in Kr-pok knockout murine embryonic fibroblasts. Coimmunoprecipitation, GST fusion protein pull-down, and immunocytochemistry assays show that the zinc-finger domain of Kr-pok interacts directly with the bZIP DNA binding domain of SREBP-1. Electrophoretic mobility shift assay, oligonucleotide pull-down, and chromatin immunoprecipitation assays showed that Kr-pok changes the transcription factor binding dynamics of Sp1 and SREBP-1c to the SRE/E-box elements of the proximal promoter. We found that Kr-pok expression increased during 3T3-L1 preadipocyte differentiation and that FASN expression is decreased by the knockdown of Kr-pok. Kr-pok facilitates the SREBP-1c-mediated preadipocyte differentiation and/or fatty acid synthesis. Kr-pok may act as an important regulator of fatty acid synthesis and may induce rapid cancer cell proliferation by increasing palmitate synthesis.
Files in This Item:
T201200679.pdf Download
DOI
22331133
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Koh, Dong In(고동인)
Kim, Min Kyeong(김민경)
Yoon, Jae Hyeon(윤재현)
Jeon, Bu Nam(전부남)
Choi, Won Il(최원일)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90939
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