Another Broken Heart
| Autor: | Jan Lammerding, Valerie L. R. M. Verstraeten |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Circulation Research. 106:234-237 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.109.212001 |
| Popis: | See related articles, pages 346–353 More than one-third of cases of dilated cardiomyopathy (DCM) are caused by inherited mutations, with 5% to 10% of these mutations being linked to the LMNA gene encoding the nuclear envelope proteins lamin A and C.1–3 Whereas geneticists have mostly looked for mutations in genes encoding sarcomeric and cytoskeletal proteins in the past, genes for nuclear envelope associated proteins are proving to be equally important candidate genes for DCM. The subsequent discoveries that mutations in other nuclear envelope proteins that directly bind to lamins A/C, for example, nesprin4 and emerin,5 can also cause DCM has stimulated the interest in exploring the role of lamin and its binding partners in DCM. New insights into the functional mechanisms by which nuclear proteins can cause DCM have come from the identification of a mutation in another lamin A/C binding partner, the nuclear protein lamina-associated polypeptide (LAP)2α, as a cause for DCM in a large kindred6 and subsequent studies in LAP2α-deficient ( LAP2 α−/−) mice.7 In this issue of Circulation Research , Gotic et al report that young, male, LAP2 α−/− mice develop systolic dysfunction and show deregulation of the major cardiac transcription factors GATA4 and myocyte enhancer factor (MEF)2c.8 These findings, taken together with previous reports showing an important role of lamin A/C in regulating gene expression by sequestering or altering the activity of transcription factors,9–11 suggest that (nucleoplasmic) lamins may act as a scaffold for transcription factors and other DNA binding proteins such as LAP2α and, through this complex, modulate gene expression and cell function. This function could be distinct or overlapping with their role in providing nuclear structure and support.12 The nuclear envelope has gained particularly great interest because mutations in its … |
| Databáze: | OpenAIRE |
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