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

Journal of Lipid Research
Bu-Nam JeonMan-Wook Hur

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 fatt...Continue Reading

References

Jul 15, 1994·Genes & Development·V J Bardwell, R Treisman
Feb 14, 1998·The Journal of Clinical Investigation·J B KimB M Spiegelman
Jun 3, 2000·Nature Genetics·M BarnaP P Pandolfi
May 8, 2002·The Journal of Clinical Investigation·Jay D HortonMichael S Brown
Jan 22, 2003·Journal of Cutaneous Pathology·D InnocenziS Calvieri
Mar 21, 2003·Biochemical and Biophysical Research Communications·Johannes V SwinnenGuido Verhoeven
Jan 1, 2004·The Journal of Biological Chemistry·Matthias LaudesStephen O'Rahilly
Jan 31, 2004·Gynecologic Oncology·Valeria SebastianiPiero Luigi Alo
May 25, 2004·Nature Genetics·José A CostoyaPier Paolo Pandolfi
Dec 4, 2004·Nature·Ryan T Phan, Riccardo Dalla-Favera
Jan 22, 2005·Nature·Takahiro MaedaPier Paolo Pandolfi
Feb 25, 2005·Lipids·Subrahmanyam S Chirala, Salih J Wakil
Mar 3, 2006·Molecular and Cellular Biochemistry·Leslie C Costello, Renty B Franklin
Sep 26, 2006·Trends in Cell Biology·Kevin F Kelly, Juliet M Daniel
Mar 27, 2007·Briefings in Functional Genomics & Proteomics·Jose A Costoya
Sep 21, 2007·Nature Reviews. Cancer·Javier A Menendez, Ruth Lupu

❮ Previous
Next ❯

Citations

Sep 13, 2012·Journal of Lipid Research·Elizebeth C Turner, B Therese Kinsella
Jan 17, 2015·International Journal of Molecular Sciences·Jiangjiang ZhuYanhong Cao
Jul 18, 2015·Biochimica Et Biophysica Acta·Dong-In KohMan-Wook Hur
May 6, 2015·Prostaglandins & Other Lipid Mediators·Helen M Reid, B Therese Kinsella
Dec 15, 2012·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Sunil K JoshiBrian T Feeley
Oct 21, 2016·Biochimica Et Biophysica Acta·Bu-Nam JeonMan-Wook Hur
Dec 3, 2016·Chemical & Pharmaceutical Bulletin·Takaaki SakaiTsuyoshi Miura
Nov 7, 2015·Stroke; a Journal of Cerebral Circulation·Rose DuScott T Weiss
Sep 1, 2017·Cellular and Molecular Life Sciences : CMLS·Avinash SrivastavaRakesh K Mishra
Aug 21, 2019·International Journal of Molecular Sciences·Víctor Jiménez-GonzálezAlbert García-Quintanilla
Oct 8, 2020·Pathology, Research and Practice·Yijiao YuanZuohui Zhao

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.