Abstract
Lamin A mutations cause many diseases, including cardiomyopathies and Progeria Syndrome. The covalent attachment of small ubiquitin-like modifier (SUMO) polypeptides regulates the function of many proteins. Until now, no examples of human disease-causing mutations that occur within a sumoylation consensus sequence and alter sumoylation were known. We show that lamin A is sumoylated at lysine 201 and that two lamin A mutants associated with familial dilated cardiomyopathy, E203G and E203K, exhibit decreased sumoylation. E203 occupies the conserved +2 position in the sumoylation consensus Psi KXE. Lamin A mutants E203G, E203K, and K201R all exhibit a similar aberrant subcellular localization and are associated with increased cell death. Fibroblasts from an individual with the E203K lamin A mutation also exhibit decreased lamin A sumoylation and increased cell death. These results suggest that SUMO modification is important for normal lamin A function and implicate an involvement for altered sumoylation in the E203G/E203K lamin A cardiomyopathies.
Document Type
Article
Publication Date
7-7-2008
Digital Object Identifier (DOI)
http://dx.doi.org/10.1083/jcb.200712124
Repository Citation
Zhang, Yu-Qian and Sarge, Kevin D., "Sumoylation Regulates Lamin A Function and is Lost in Lamin A Mutants Associated with Familial Cardiomyopathies" (2008). Molecular and Cellular Biochemistry Faculty Publications. 56.
https://uknowledge.uky.edu/biochem_facpub/56
Table S1
Notes/Citation Information
Published in The Journal of Cell Biology, v. 182, no. 1, p. 35-39.
© 2008 Zhang et al.
Beginning six months after publication, RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.