Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies

Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which...

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Bibliographic Details
Published in:Nucleus (Austin, Tex.) Tex.), 2020-01, Vol.11 (1), p.299-314
Main Authors: Liu, Sunny Yang, Ikegami, Kohta
Format: Article
Language:English
Subjects:
c-Jun
cardiomyopathies
cdk1
chromatin
chromosome
enhancer
farnesylation
interphase
lamin A/C
lamina-associated domain
laminopathies
lmna
mitosis
muscular dystrophy
nuclear interior
Nuclear lamin
phosphorylation
progeria
Review
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Summary:Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins' function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins' function in the nuclear interior.
ISSN:1949-1034
1949-1042
DOI:10.1080/19491034.2020.1832734