title: Repression of the RHOH gene by JunD.
abstract: RhoH is a member of the Rho family of small GTP-binding proteins that lacks GTPase activity. Since RhoH is constantly bound by GTP, it is thought to be constitutively active and controlled predominantly by changes in quantitative expression. RhoH is produced specifically in haematopoietic cells and aberrant expression has been linked to various forms of leukaemia. Transcription of the RHOH gene is the first level at which the quantitative levels of the RhoH protein are regulated. Previous studies have demonstrated that RHOH gene transcription is initiated by three distinct promoter regions designated P1, P2 and P3 that define the 5' end of exons 1, 2 and 4 respectively. In the present study we report that the P3 promoter is largely responsible for RHOH gene transcription in the B-lymphocytic cell line Raji. The P3 promoter contains a minimal promoter region and a repressor region extending from -236 to +67 and +68 to +245 respectively, relative to the 5' end of exon 4. Chromatin immunoprecipitation demonstrated that two AP1 (activator protein 1) sites in the minimal promoter region bind JunD. When JUND is overexpressed, the endogenous RHOH gene is repressed; however, when JUND is inhibited, expression of endogenous RHOH is induced both in the Raji cell line and AML (acute myeloid leukaemia) cells. In the HCL (hairy cell leukaemia) cell line JOK-1, induction of RHOH increases expression of the α isoform of protein kinase C. This downstream target of RHOH is also induced in AML cells by JUND inhibition. Collectively, these data indicate that JunD is an inhibitor of RHOH gene expression.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U.837, Centre Jean-Pierre Aubert, Institut pour la Recherche sur le Cancer de Lille and Université Lille Nord de France, UDSL, 59000 Lille, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Delestré
authors.forename: Céline
authors.initials: C
authors.lastname: Berthon
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesnel
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kerckaert
authors.forename: Sylvie
authors.initials: S
authors.lastname: Galiègue-Zouitina
authors.forename: Carl Simon
authors.initials: CS
authors.lastname: Shelley
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: C559371:JunD protein, human; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; C447841:RhoH protein, human; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins