Going Out on a LIM and Cysteine-Rich Domains 1 Limb

Abstract

Hypertension induces cardiac myocytes in the left ventricle to activate a hypertrophic response that involves the upregulation of contractile proteins and the re-expression of fetal genes.1 Transcriptional induction is an important component of this response, and the zinc finger-containing transcription factors GATA4 and GATA6 have been shown to directly stimulate cardiac hypertrophy.2 LIM domain proteins (named after the first 3 LIM proteins identified: Lin11, Isl-1, and Mec-3) interact with transcriptional regulators, kinases, and structural proteins. Because of these protein-protein interactions, LIM domain proteins have been assigned roles in cell growth, differentiation, and cytoskeletal remodeling.3 Several LIM proteins have been identified by proteomic and functional screens of left ventricles subjected to pressure overload.4,5 LIM and cysteine-rich domains 1 (Lmcd1) protein has 2 LIM domains in the C-terminus and a cysteine-rich domain in the N-terminus. Because it contains ≥1 LIM domain in the C-terminus, Lmcd1 is classified as a group 3 LIM protein, and most of the previously identified group 3 LIM proteins have been shown to localize to the cytoplasm. Lmcd1 is expressed in most tissues and is particularly highly expressed in cardiac and skeletal muscle.6 Beyond a …