title: Stra13 and Sharp-1, the non-grouchy regulators of development and disease.
abstract: Stra13 and Sharp-1 are transcriptional repressors that share domain structure similarity with members of the basic helix-loop-helix-Orange subfamily. In contrast to other members that include Hes and Hey proteins, transcriptional repression mediated by Stra13 and Sharp-1 does not involve recruitment of the corepressor Groucho. Both proteins undergo sumoylation at evolutionarily conserved sites, and this posttranslational modification serves as a platform for association with chromatin-modifying enzymes including histone deacetylases and histone methyltransferases. In addition to being widely expressed during embryonic development and in adult tissues, the expression of both genes is induced by a number of stimuli. Loss-of-function and gain-of-function studies have demonstrated their function in cellular differentiation and regeneration, in regulation of circadian rhythms, immune homeostasis, and metabolism. Given their diverse physiological functions in several tissues, it is not surprising that deregulated expression of Stra13 and Sharp-1 is apparent in human pathologies. Here, we review our current understanding of their cellular functions that suggest a requirement in maintenance of tissue homeostasis.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Jin Rong
authors.initials: JR
authors.lastname: Ow
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yong Hua
authors.initials: YH
authors.lastname: Tan
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Avinash G
authors.initials: AG
authors.lastname: Bahirvani
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore. Electronic address: phsrt@nus.edu.sg.
authors.forename: Reshma
authors.initials: R
authors.lastname: Taneja
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006655:Histone Deacetylases / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007107:Immune System / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C422085:BHLHE41 protein, human; C470968:Bhlhb3 protein, mouse; C491539:Bhlhe40 protein, mouse; C551977:CENPX protein, human
keywords: Apoptosis; Cancer; Chromatin; Differentiation; G9a; HDAC1; Immune system; Regeneration; Skeletal muscle; Sumoylation; bHLHB2; bHLHB3; bHLHE40