Histone deacetylase inhibition-mediated post-translational elevation of p27KIP1 protein levels is required for G1 arrest in fibroblasts

Journal of Cellular Physiology
James S Chen, D V Faller

Abstract

Butyrate, a non-toxic short-chain fatty acid (SCFA) and inhibitor of histone deacetylase (HDAC), has potential as an anti-tumor agent because it imposes a reversible G1 block in normal cells yet induces apoptosis in tumor lines. As a potent reactivator of fetal globin transcription, butyrate is used clinically in the treatment of hemoglobinopathies. The anti-proliferative effect of butyrate and its derivatives on in vivo erythroid cell maturation, however, has limited their utility. The molecular mechanisms underlying the G1 arrest induced by butyrate and related SCFAs remain unclear. One model, drawing on tumor cell data, proposes that HDAC inhibition and subsequent transcriptional induction of cyclin-dependent kinase inhibitor (CKI) p21CIP are required. However, because of potentially confounding genetic mutations present in tumor models, we examined SCFA effects on CKIs in a non-transformed growth control model. Using murine 3T3 fibroblasts, we find p27KIP1 is also strongly induced. Unlike previously described effects of butyrate and HDAC inhibition on p21CIP, p27KIP1 induction did not occur at the transcriptional level; instead, the stability of the p27KIP1 protein increased. Other structurally unrelated HDAC inhibitors, in...Continue Reading

References

Feb 1, 1976·In Vitro·K N Prasad, P K Sinha
May 1, 1978·Cell·L Sealy, R Chalkley
Apr 17, 1992·Science·S O Freytag, T J Geddes
Jan 1, 1990·Annals of the New York Academy of Sciences·S P PerrineY W Kan
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·S P PerrineY W Kan
Jan 1, 1989·Advances in Experimental Medicine and Biology·S P PerrineY W Kan
Feb 7, 1985·The New England Journal of Medicine·S P PerrineD V Faller
Nov 3, 1989·Science·A B Pardee
Oct 1, 1987·Journal of Cellular Physiology·A Hirschfeld, J Bressler
Jan 1, 1983·Journal of Cellular Biochemistry·E WintersbergerU Wintersberger
Jan 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·J CampisiA B Pardee
Jan 14, 1993·The New England Journal of Medicine·S P PerrineN F Olivieri
Aug 2, 1996·The Journal of Biological Chemistry·N RivardJ Pouysségur
Feb 12, 1998·Biochimica Et Biophysica Acta·Y Zhang, S C Lin
Mar 1, 1995·Current Opinion in Hematology·D V Faller, S P Perrine
Jan 1, 1997·Annual Review of Cell and Developmental Biology·D O Morgan
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·S Y ArcherR A Hodin
Jun 17, 1998·Blood Cells, Molecules & Diseases·S J MentzerD V Faller
Nov 12, 1998·Trends in Biochemical Sciences·P Russell
Feb 23, 1999·The American Journal of Pathology·R V LloydB W Scheithauer
Mar 11, 1999·Current Opinion in Genetics & Development·T Kouzarides
Mar 12, 1999·Annual Review of Medicine·J TsihliasJ Slingerland
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·S RaoK Keyomarsi
Nov 13, 1999·Nature Cell Biology·A C CarranoM Pagano
Jan 15, 2000·The Journal of Biological Chemistry·N GuoC Vaziri
Feb 17, 2000·The EMBO Journal·M A Martínez-BalbásT Kouzarides
Mar 4, 2000·Journal of Cellular Physiology·A SgambatoI B Weinstein
Feb 7, 2001·The Journal of Biological Chemistry·G MarzioM Giacca

❮ Previous
Next ❯

Citations

Apr 3, 2009·Journal of the Association for Research in Otolaryngology : JARO·Eric L SlatteryMark E Warchol
Feb 10, 2011·Journal of Clinical Immunology·Xiaorong ZhouXiaoying Wang
Jun 15, 2011·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yuhui LiGang Wu
Jul 9, 2010·Anti-cancer Drugs·Andrea UeckerFrank-D Böhmer
Jan 15, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Hannes M FindeisenDennis Bruemmer
Jul 22, 2009·Progress in Neurobiology·Wei WangDeding Tao
Oct 17, 2018·The Biochemical Journal·Carrie DraneyJeffery S Tessem
Mar 2, 2011·Expert Opinion on Therapeutic Targets·Adriana BorrielloFulvio Della Ragione
Nov 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carmen A BanuelosPeggy L Olive
Jun 26, 2007·Bioorganic & Medicinal Chemistry Letters·Shoukou LeeHiroyuki Miyachi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis