title: Proliferative status regulates HDAC11 mRNA abundance in nontransformed fibroblasts.
abstract: Histone deacetylases (HDACs) are important determinants of gene transcription and other biological processes. HDAC11 is one of the least characterized HDACs and is the only member of the class IV HDAC family. Our studies examined the events that control the expression of the HDAC11 transcript. We show that platelet-derived growth factor (PDGF) rapidly reduces the abundance of HDAC11 mRNA when added to density-arrested Balb/c-3T3 cells, which are nontransformed fibroblasts. Reduction required mRNA and protein synthesis, but not AKT or ERK activity, and resulted from accelerated turnover of the HDAC11 transcript. Reduction was transient in cells receiving PDGF alone but sustained in cells receiving both PDGF and platelet-poor plasma, which together promote G₀/G₁ traverse and S phase entry. Plasma alone did not appreciably reduce HDAC11 mRNA abundance, nor did epidermal growth factor, insulin-like growth factor, or insulin. HDAC11 mRNA accumulated in Balb/c-3T3 cells exiting the cell cycle due to density-dependent growth inhibition or serum deprivation. Of note, HDAC11 mRNA did not accumulate in a spontaneously transformed Balb/c-3T3 clonal variant (clone 2) that does not density arrest. The HDAC11 promoter was active in Balb/c-3T3 but not clone 2 cells; inactivity in clone 2 cells did not result from methylation of CpG islands. Overexpression of HDAC11 inhibited the cell cycle progression of both transformed and nontransformed fibroblasts. Our studies identify the HDAC11 transcript as a PDGF target and show that HDAC11 mRNA abundance correlates inversely with proliferative status.
authors.affiliation: Department of Molecular Oncology and Gonzmart Research Laboratory; H. Lee Moffitt Cancer Center & Research Institute; Tampa, FL USA.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Bagui
authors.forename: Savitha S
authors.initials: SS
authors.lastname: Sharma
authors.forename: Le
authors.initials: L
authors.lastname: Ma
authors.forename: W Jack
authors.initials: WJ
authors.lastname: Pledger
mesh_terms: D000818:Animals; D002452:Cell Count; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007328:Insulin; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D013002:Somatomedins; D004815:Epidermal Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C528111:Hdac11 protein, mouse; D006655:Histone Deacetylases
keywords: cell cycle; clone 2; fibroblasts; histone deacetylase 11; platelet-derived growth factor
references.citation: Proc Natl Acad Sci U S A. 1990 Mar;87(5):1663-7
references.pmid: 1689846
references.citation: Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481-5
references.pmid: 270695
references.citation: Proc Natl Acad Sci U S A. 1981 Jul;78(7):4358-62
references.pmid: 6170062
references.citation: Gene Expr. 1996;5(4-5):245-53
references.pmid: 8723390
references.citation: J Biol Chem. 2002 Jul 12;277(28):25748-55
references.pmid: 11948178
references.citation: Blood. 2011 Mar 10;117(10):2910-7
references.pmid: 21239696
references.citation: Horm Metab Res. 2013 Feb;45(2):159-68
references.pmid: 22990992
references.citation: Glia. 2009 Jan 1;57(1):1-12
references.pmid: 18627006
references.citation: Int J Mol Med. 2005 Oct;16(4):589-98
references.pmid: 16142391
references.citation: Physiol Genomics. 2000 Apr 27;2(3):143-7
references.pmid: 11015593
references.citation: Oncogene. 2007 Aug 13;26(37):5541-52
references.pmid: 17694093
references.citation: Cell Cycle. 2009 Jan 1;8(1):115-24
references.pmid: 19158484
references.citation: Clin Exp Pharmacol Physiol. 2012 Sep;39(9):751-8
references.pmid: 22651689
references.citation: J Neurosci Res. 2008 Feb 15;86(3):537-43
references.pmid: 17893925
references.citation: Int J Cancer. 2013 May 1;132(9):2200-8
references.pmid: 23024001
references.citation: Physiol Rev. 1999 Oct;79(4):1283-316
references.pmid: 10508235
references.citation: Int J Cancer. 2007 Apr 15;120(8):1664-8
references.pmid: 17230502
references.citation: Nat Rev Mol Cell Biol. 2008 Mar;9(3):206-18
references.pmid: 18292778
references.citation: J Biol Chem. 2001 Nov 30;276(48):44905-11
references.pmid: 11555648
references.citation: J Biol Chem. 2009 Apr 24;284(17):11446-53
references.pmid: 19276081
references.citation: Nat Immunol. 2009 Jan;10(1):92-100
references.pmid: 19011628
references.citation: Nat Rev Genet. 2012 May 29;13(7):484-92
references.pmid: 22641018
references.citation: Mol Cell. 2007 Jul 20;27(2):197-213
references.pmid: 17643370
references.citation: J Surg Res. 2012 May 15;174(2):359-68
references.pmid: 21392795
references.citation: Bioinformatics. 2002 Dec;18(12):1593-9
references.pmid: 12490443