title: Genes, proteins and complexes: the multifaceted nature of FHL family proteins in diverse tissues.
abstract: Four and a half LIM domain protein 1 (FHL1) is the founding member of the FHL family of proteins characterized by the presence of four and a half highly conserved LIM domains. The LIM domain is a protein-interaction motif and is involved in linking proteins with both the actin cytoskeleton and transcriptional machinery. To date, more than 25 different protein interactions have been identified for full length FHL1 and its spliced variants, and these interactions can be mapped to a variety of functional classes. Because FHL1 is expressed predominantly in skeletal muscle, all of these proteins interactions translate into a multifunctional and integral role for FHL1 in muscle development, structural maintenance, and signalling. Importantly, 27 FHL1 genetic mutations have been identified that result in at least six different X-linked myopathies, with patients often presenting with cardiovascular disease. FHL1 expression is also significantly up-regulated in a variety of cardiac disorders, even at the earliest stages of disease onset. Alternatively, FHL1 expression is suppressed in a variety of cancers, and ectopic FHL1 expression offers potential for some phenotype rescue. This review focuses on recent studies of FHL1 in muscular dystrophies and cardiovascular disease, and provides a comprehensive review of FHL1s multifunctional roles in skeletal muscle.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.
authors.forename: Thiruchelvi
authors.initials: T
authors.lastname: Shathasivam
authors.forename: Thomas
authors.initials: T
authors.lastname: Kislinger
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Gramolini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D051880:Receptors, Notch