Modulation of cardiac growth and development by HOP, an unusual homeodomain protein.
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.
Shin
Chong Hyun
CH
Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Liu
Zhi-Ping
ZP
Passier
Robert
R
Zhang
Chun-Li
CL
Wang
Da-Zhi
DZ
Harris
Thomas M
TM
Yamagishi
Hiroyuki
H
Richardson
James A
JA
Childs
Geoffrey
G
Olson
Eric N
EN
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
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