{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:17:26Z","timestamp":1793042246125,"version":"4.5.0"},"reference-count":69,"publisher":"American Society for Cell Biology (ASCB)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by &gt;300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype\u2013phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A\u2013binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome\u2013wide ORFeome library, we identified and validated 337 lamin A\u2013binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson\u2013Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)\u2013like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein\u2013protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes.<\/jats:p>","DOI":"10.1091\/mbc.e14-02-0733","type":"journal-article","created":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T02:21:45Z","timestamp":1394677305000},"page":"1493-1510","source":"Crossref","is-referenced-by-count":77,"title":["Systematic identification of pathological lamin A interactors"],"prefix":"10.1091","volume":"25","author":[{"given":"Travis A.","family":"Dittmer","sequence":"first","affiliation":[{"name":"National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Sahni","sequence":"additional","affiliation":[{"name":"Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215"},{"name":"Department 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