2016
DOI: 10.18632/aging.100903
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Abstract: Mutants of lamin A cause diseases including the Hutchinson-Gilford progeria syndrome (HGPS) characterized by premature aging. Lamin A undergoes a series of processing reactions, including farnesylation and proteolytic cleavage of the farnesylated C-terminal domain. The role of cleavage is unknown but mutations that affect this reaction lead to progeria. Here we show that interphase serine 22 phosphorylation of endogenous mutant lamin A (progerin) is defective in cells from HGPS patients. This defect can be mim… Show more

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Cited by 18 publications
(57 citation statements)
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References 46 publications
(57 reference statements)
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“…Phosphorylation of lamin A facilitates disassembly of lamin filaments and breakdown of the nuclear lamina in preparation for mitosis (Snider and Omary 2014). In HGPS cells, phosphorylation of a prominent site (S22) by CDK1 during interphase is reduced, and prenylation inhibitors can rescue this defect (Moiseeva, Lopes-Paciencia et al 2016). Moreover, preventing phosphorylation of lamin A/progerin by CDK inhibitors accelerates senescence in HGPS fibroblasts.…”
Section: Hgps Is Caused By Expression Of a Mutant Lamin A Protein mentioning
confidence: 99%
“…Phosphorylation of lamin A facilitates disassembly of lamin filaments and breakdown of the nuclear lamina in preparation for mitosis (Snider and Omary 2014). In HGPS cells, phosphorylation of a prominent site (S22) by CDK1 during interphase is reduced, and prenylation inhibitors can rescue this defect (Moiseeva, Lopes-Paciencia et al 2016). Moreover, preventing phosphorylation of lamin A/progerin by CDK inhibitors accelerates senescence in HGPS fibroblasts.…”
Section: Hgps Is Caused By Expression Of a Mutant Lamin A Protein mentioning
confidence: 99%
“…Phosphorylation of human lamin A/C at Ser22 in the N-terminal head and Ser392 proximal to the C-terminal end of the rod (and analogous sites in lamin B) is required for lamina disassembly during mitosis (Heald and McKeon, 1990). These amino acid residues are targeted by cyclin-dependent kinase 1 (Cdk1) (Ward and Kirschner, 1990) and, possibly, other kinases, including Cdk5 (Chang et al, 2011), Cdk4 and Cdk6 (Moiseeva et al, 2016), as well as extracellular signal-regulated kinases 1 and 2 (Erk1 and Erk2; officially known as MAPK2 and MAPK1, respectively) (Peter et al, 1992), which may target these sites also during interphase (Kochin et al, 2014). Furthermore, lamin A variants with phosphomimetic Ser-to-Asp mutations at these sites localized to the nuclear interior in interphase cells and were highly mobile and easily extractable with non-ionic detergents (Kochin et al, 2014), suggesting that phosphorylation at previously known mitosis-specific sites regulates lamin assembly state and intranuclear localization also during interphase.…”
Section: Regulation Of A-type Lamins In the Nuclear Interiormentioning
confidence: 99%
“…Because lamin A is also a component of the internal nuclear matrix (Vlcek & Foisner, ), and because progerin has been shown to heterodimerize with wild‐type A‐ and B‐type lamins (Delbarre et al , ), nucleoplasmic progerin accumulation might affect the distribution and/or the organization of nuclear structures such as nucleoli, speckles, and different nuclear bodies. Moreover, the localization of progerin into intranuclear aggregates in HGPS fibroblast cells was often reported (Goldman et al , ; Moiseeva et al , ). Promyelocytic leukemia nuclear bodies (PML‐NBs) are discrete nuclear speckles tightly associated with the nuclear matrix (Ascoli & Maul, ) and implicated in cellular senescence (Ferbeyre, ), whose nuclear arrangement was shown to be influenced by A‐type lamin deficiency (Stixova et al , ).…”
Section: Introductionmentioning
confidence: 96%