Modulation of cardiac growth and development by HOP, an unusual homeodomain protein

Cell. 2002 Sep 20;110(6):725-35. doi: 10.1016/s0092-8674(02)00933-9.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Female
  • Gene Expression Regulation, Developmental
  • Heart / anatomy & histology
  • Heart / embryology*
  • Heart / growth & development*
  • Heart / physiopathology
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Homeodomain Proteins / physiology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Models, Biological
  • Molecular Sequence Data
  • Myocardium / metabolism
  • Phenotype
  • Sequence Alignment
  • Serum Response Factor / metabolism
  • Transcription Factors*
  • Xenopus Proteins*

Substances

  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • Hop protein, mouse
  • NKX2-5 protein, human
  • Nkx2-5 protein, mouse
  • Serum Response Factor
  • Transcription Factors
  • Xenopus Proteins

Associated data

  • GENBANK/AF534182