title: Modulation of cardiac growth and development by HOP, an unusual homeodomain protein.
abstract: We have discovered an unusual homeodomain protein, called HOP, which is comprised simply of a homeodomain. HOP is highly expressed in the developing heart where its expression is dependent on the cardiac-restricted homeodomain protein Nkx2.5. HOP does not bind DNA and acts as an antagonist of serum response factor (SRF), which regulates the opposing processes of proliferation and myogenesis. Mice homozygous for a HOP null allele segregate into two phenotypic classes characterized by an excess or deficiency of cardiac myocytes. We propose that HOP modulates SRF activity during heart development; its absence results in an imbalance between cardiomyocyte proliferation and differentiation with consequent abnormalities in cardiac morphogenesis.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Chong Hyun
authors.initials: CH
authors.lastname: Shin
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liu
authors.forename: Robert
authors.initials: R
authors.lastname: Passier
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Zhang
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Harris
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamagishi
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Childs
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development* / Q000503:physiopathology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D010641:Phenotype; D016415:Sequence Alignment; D026362:Serum Response Factor / Q000378:metabolism; D014157:Transcription Factors; D029867:Xenopus Proteins
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C466740:Hop protein, mouse; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; D026362:Serum Response Factor; D014157:Transcription Factors; D029867:Xenopus Proteins