title: CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy.
abstract: BACKGROUND
  Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart cause increased size (hypertrophic growth) of cardiomyocytes. Whereas the regulatory pathways that activate cardiac hypertrophy have been well-established, the molecular events that inhibit or repress cardiac hypertrophy are less known.
  
  
  OBJECTIVE
  To identify and investigate novel regulators that modulate cardiac hypertrophy.
  
  
  RESULTS
  Here, we report the identification, characterization, and functional examination of a novel cardiac Isl1-interacting protein (CIP). CIP was identified from a bioinformatic search for novel cardiac-expressed genes in mouse embryonic hearts. CIP encodes a nuclear protein without recognizable motifs. Northern blotting, in situ hybridization, and reporter gene tracing demonstrated that CIP is highly expressed in cardiomyocytes of developing and adult hearts. Yeast two-hybrid screening identified Isl1, a LIM/homeodomain transcription factor essential for the specification of cardiac progenitor cells in the second heart field, as a cofactor of CIP. CIP directly interacted with Isl1, and we mapped the domains of these two proteins, which mediate their interaction. We show that CIP represses the transcriptional activity of Isl1 in the activation of the myocyte enhancer factor 2C. The expression of CIP was dramatically reduced in hypertrophic cardiomyocytes. Most importantly, overexpression of CIP repressed agonist-induced cardiomyocyte hypertrophy.
  
  
  CONCLUSIONS
  Our studies therefore identify CIP as a novel regulator of cardiac hypertrophy.
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Harvard Medical School, MA 02115, USA.
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Huang
authors.forename: Hee
authors.initials: H
authors.lastname: Young Seok
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Jinghai
authors.initials: J
authors.lastname: Chen
authors.forename: Jian-Fu
authors.initials: JF
authors.lastname: Chen
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Tao
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D006332:Cardiomegaly / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D056970:Co-Repressor Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015723:Gene Library; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D009687:Nuclear Proteins; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D060850:LIM-Homeodomain Proteins; C559899:MLIP protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1