Biology and Regulatory Roles of Nuclear Lamins in Cellular Function and Dysfunction

Author(s): Syeda G. Khadija, Fei Chen, Timothy Hadden, Randall L. Commissaris, Anjaneyulu Kowluru.

Journal Name: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Under Re-organization)

Volume 9 , Issue 2 , 2015

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Abstract:

Nuclear lamins, namely lamins A, B and C, surround the nucleoplasmic contents in a meshlike network called the nuclear lamina. These intermediate filaments provide a structural framework to the nuclear envelope (NE), play a role in arrangement of the chromatin within the nucleus, in DNA replication and also participate in DNA damage repair. In order for lamins to be involved in these important nuclear processes and to be functionally active, they undergo a series of post-translational modifications (farnesylation, endoproteolytic cleavage, carboxylmethylation etc.), of which farnesylation is the most studied. Improper farnesylation of lamin proteins, especially lamin A, leads to a number of diseases affecting the striated muscle (e.g. Emery- Dreifuss Muscular Dystrophy, Dilated Cardiomyopathy), adipose tissue (e.g. Dunnigan-type familial partial lipodystrophy) and could result in abnormal senescence and growth deformities (e.g. Progeria syndrome); these are referred to as laminopathies. Despite the existing literature and evidence regarding functions of lamins and diseases associated with abnormal lamin processing, a lot remains to be understood in regards to lamin biology and their role as potential therapeutic targets. In this brief review, we have attempted to summarize the roles of lamins in physiology and pathology of the cell and in type 2 diabetes mellitus [T2DM] and also enlisted patents on methods, systems and devices developed for improving pancreatic beta cell function in diabetes mellitus.

Keywords: Farnesylation, lamina, lamin A/C, lamin B, laminopathy, nuclear lamins.

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Article Details

VOLUME: 9
ISSUE: 2
Year: 2015
Page: [111 - 120]
Pages: 10
DOI: 10.2174/1872214809666151009120402
Price: $58

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