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