Kr-pok Increases FASN Expression by Modulating the DNA Binding of SREBP-1c and Sp1 at the Proximal Promoter

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2012 Feb 15

PMID 22331133

Citations 13

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

Affiliations

Soon will be listed here.

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.

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