Sumoylation delimits KLF8 transcriptional activity associated with the cell cycle regulation

The Journal of Biological Chemistry
Huijun WeiJ Zhao

Abstract

KLF8 (Krüppel-like factor 8) is a member of the Krüppel transcription factor family that binds CACCC elements in DNA and activates or represses their target genes in a context-dependent manner. Here we present sumoylation as a novel mechanism that regulates KLF8 post-translationally. We found that KLF8 can be covalently modified by small ubiqitin-like modifier (SUMO)-1, SUMO-2, and SUMO-3 in vivo. We showed that KLF8 interacted with the PIAS family of SUMO E3 ligases PIAS1, PIASy, and PIASxalpha but not with E2 SUMO-conjugating enzyme Ubc9. Furthermore, we demonstrated that the E2 and E3 ligases enhanced the sumoylation of KLF8. In addition, site-directed mutagenesis identified lysine 67 as the major sumoylation site on KLF8. Lysine 67 to arginine mutation strongly enhanced activity of KLF8 as a repressor or activator to its physiological target promoters and as an inducer of the G(1) cell cycle progression. Taken together, our results demonstrated that sumoylation of KLF8 negatively regulates its transcriptional activity and cellular functions.

References

Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·H C Chen, J L Guan
Dec 31, 1997·Science·C D ChungK Shuai
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·B LiuK Shuai
Sep 12, 1998·Molecular Cell·J M DesterroR T Hay
Dec 29, 1998·The Journal of Cell Biology·J H ZhaoJ L Guan
Jul 20, 1999·Molecular and Cellular Biology·A DoetzlhoferC Seiser
Aug 24, 1999·Nucleic Acids Research·S Philipsen, G Suske
Dec 1, 1999·The Journal of Cell Biology·E S Johnson, G Blobel
Feb 29, 2000·The Journal of Biological Chemistry·H Saitoh, J Hinchey
May 2, 2000·The Journal of Biological Chemistry·S MullerA Dejean
Oct 14, 2000·Annual Review of Cell and Developmental Biology·F Melchior
Jan 2, 2001·The Journal of Biological Chemistry·M S RodriguezR T Hay
Mar 27, 2001·Nature Reviews. Molecular Cell Biology·S MüllerS Jentsch
Apr 5, 2001·Molecular and Cellular Biology·X Chen, J J Bieker
May 10, 2001·Trends in Biochemical Sciences·R T Hay
Jun 26, 2001·Journal of Cellular Physiology·A R BlackJ Azizkhan-Clifford
Jul 10, 2001·The Journal of Biological Chemistry·J J Bieker
Jul 14, 2001·The Journal of Biological Chemistry·M H TathamR T Hay
Jan 17, 2002·Cell·Andrea PichlerFrauke Melchior
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Darja Schmidt, Stefan Müller
Nov 13, 2002·The Journal of Biological Chemistry·Hong S YoonVincent W Yang
Nov 15, 2002·Cancer Biology & Therapy·Dania Alarcon-Vargas, Ze'ev Ronai
Mar 4, 2003·EMBO Reports·Alexis VergerMerlin Crossley
Mar 7, 2003·Genome Biology·Joanna KaczynskiRaul Urrutia
Apr 8, 2003·Cell·Michael H KageyDavid Wotton
Sep 23, 2003·The Journal of Biological Chemistry·Gress KadaréJean-Antoine Girault
Apr 6, 2004·Science·Joan S SteffanJ Lawrence Marsh
May 1, 2004·The Journal of Biological Chemistry·Yasuhito TeruiJunying Yuan
Jun 11, 2004·Annual Review of Biochemistry·Erica S Johnson
Feb 3, 2005·Molecular and Cellular Biology·José PerdomoMerlin Crossley
Apr 6, 2005·Molecular Cell·Ronald T Hay

❮ Previous
Next ❯

Citations

Sep 4, 2009·Cell Research·Estefanía Rodríguez, John A Martignetti
Oct 30, 2012·The Journal of Biological Chemistry·Heng LuJihe Zhao
Aug 9, 2008·The Journal of Biological Chemistry·Sally A EatonMerlin Crossley
Jul 19, 2011·Genes & Development·Huijun WeiJun-Lin Guan
Feb 7, 2007·Molecular and Cellular Biology·Alister P W FunnellMerlin Crossley
Oct 21, 2010·Physiological Reviews·Beth B McConnell, Vincent W Yang
Jul 26, 2013·World Journal of Gastroenterology : WJG·Wen-Fei WangChuan-Xin Wang
Oct 12, 2013·Journal of Molecular Neuroscience : MN·Ran YiQi Dong
Mar 19, 2013·Journal of Cancer Research and Clinical Oncology·Hui ZhangDaiming Fan
Jul 5, 2011·FEBS Letters·Livnat ShimshonBoaz Tirosh
Jun 3, 2008·Trends in Cell Biology·Richard K Assoian, Eric A Klein
Oct 13, 2015·Oncogene·N Godin-HeymannJ Downward
Jul 6, 2014·Frontiers in Physiology·Jeong-Ah KimHyug Moo Kwon
Dec 3, 2014·Biochimica Et Biophysica Acta·Sarwar HashmiRandy Gaugler
Mar 2, 2017·Development·Agnieszka B BialkowskaSandeep K Mallipattu
Oct 18, 2014·Biotechnology and Applied Biochemistry·Kai LiangDexiang Lu
Oct 13, 2006·The EMBO Journal·Shen-Hsi YangAndrew D Sharrocks
Jun 20, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Victoria MgbemenaSantanu Bose
Aug 16, 2017·Experimental and Therapeutic Medicine·Yifei LiuYe Tian
Mar 21, 2008·The Journal of Biological Chemistry·Xianhui WangJihe Zhao
Mar 22, 2013·The Journal of Biological Chemistry·Soroush TahmasebiXiang-Jiao Yang
Oct 18, 2007·The Journal of Biological Chemistry·Sergey ChupretaJorge A Iñiguez-Lluhí
Sep 25, 2017·Cancer Research·Huijun WeiCarlo M Croce
Aug 12, 2021·Cancer Control : Journal of the Moffitt Cancer Center·Peng ZhuWei-Jun Wang

❮ 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.