Abstract:
:Adult cardiomyocytes are irreversibly postmitotic but respond to a variety of stimuli by hypertrophic growth, which is associated with an increase in cell size and protein content, organization of sarcomeres, and activation of a fetal gene program. Recently, we described a novel cardiac helicase activated by MEF2 protein (CHAMP), which is expressed specifically in the heart throughout prenatal and postnatal development. Here we show that CHAMP acts as an inhibitor of cell proliferation and cardiomyocyte hypertrophy. Ectopic expression of CHAMP inhibits proliferation of HeLa cells and blocks cell cycle entry of serum-stimulated NIH 3T3 cells. Overexpression of CHAMP in primary neonatal cardiomyocytes blocks hypertrophic growth and the induction of fetal genes in response to stimulation by serum and phenylephrine but does not prevent sarcomere organization or early mitogenic signaling events including activation of extracellular signal-regulated kinases or up-regulation of c-fos. Inhibition of cardiomyocyte hypertrophy by CHAMP requires the conserved ATPase domain and is accompanied by up-regulation of the cyclin-dependent protein kinase inhibitor p21(CIP1). These findings identify CHAMP as a cardiac-specific suppressor of cardiomyocyte hypertrophy and cell cycle progression and suggest that CHAMP may suppress these processes through the regulation of p21(CIP1).
journal_name
Proc Natl Acad Sci U S Aauthors
Liu ZP,Olson ENdoi
10.1073/pnas.261708699keywords:
subject
Has Abstractpub_date
2002-02-19 00:00:00pages
2043-8issue
4eissn
0027-8424issn
1091-6490pii
99/4/2043journal_volume
99pub_type
杂志文章abstract::In Xenopus oocytes injected with rat brain mRNA, as in neurons, glycine greatly potentiated responses of the N-methyl-D-aspartate (NMDA) type of excitatory amino acid receptor. Injected oocytes generated a partially desensitizing inward current in response to NMDA with 30 nM added glycine. As the added glycine concent...
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更新日期:2011-08-16 00:00:00