Early in mitosis, MPF phosphorylates specific serine residues in all three nuclear lamins, causing depolymerization of the lamin intermediate filaments. The phosphorylated lamin B dimers remain associated with the nuclear membrane via their isoprenyl anchor. Lamin A is targeted to the nuclear membrane by an isoprenyl group but it is cleaved shortly after arriving at the membrane. It stays associated with the membrane through protein-protein interactions of itself and other membrane associated proteins, such as LAP1. Depolymerization of the nuclear lamins leads to disintegration of the nuclear envelope. Transfection experiments demonstrate that phosphorylation of human lamin A is required for lamin depolymerization, and thus for disassembly of the nuclear envelope, which normally occurs early in mitosis.
臨床意義
Mutations in the LMNA gene are associated with several diseases, including Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, Restrictive dermopathy and Hutchinson-Gilford progeria syndrome. A truncated version of lamin A, commonly known as progerin, causes Hutchinson-Gilford progeria syndrome.[5][6]
Kamat AK, Rocchi M, Smith DI, Miller OJ. Lamin A/C gene and a related sequence map to human chromosomes 1q12.1-q23 and 10. Somat. Cell Mol. Genet. March 1993, 19 (2): 203–8. PMID 8511676. doi:10.1007/BF01233534.
Wydner KL, McNeil JA, Lin F, Worman HJ, Lawrence JB. Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization. Genomics. March 1996, 32 (3): 474–8. PMID 8838815. doi:10.1006/geno.1996.0146.
Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE. Emerin interacts in vitro with the splicing-associated factor, YT521-B. Eur. J. Biochem. June 2003, 270 (11): 2459–66. PMID 12755701. doi:10.1046/j.1432-1033.2003.03617.x.
Sakaki M, Koike H, Takahashi N, Sasagawa N, Tomioka S, Arahata K, Ishiura S. Interaction between emerin and nuclear lamins. J. Biochem. February 2001, 129 (2): 321–7. PMID 11173535. doi:10.1093/oxfordjournals.jbchem.a002860.
Clements L, Manilal S, Love DR, Morris GE. Direct interaction between emerin and lamin A. Biochem. Biophys. Res. Commun. January 2000, 267 (3): 709–14. PMID 10673356. doi:10.1006/bbrc.1999.2023.
Barton RM, Worman HJ. Prenylated prelamin A interacts with Narf, a novel nuclear protein. J. Biol. Chem. October 1999, 274 (42): 30008–18. PMID 10514485. doi:10.1074/jbc.274.42.30008.
Lloyd DJ, Trembath RC, Shackleton S. A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum. Mol. Genet. April 2002, 11 (7): 769–77. PMID 11929849. doi:10.1093/hmg/11.7.769.
Gruenbaum Y, Wilson KL, Harel A; et al. Review: nuclear lamins--structural proteins with fundamental functions.. J. Struct. Biol. 2000, 129 (2–3): 313–23. PMID 10806082. doi:10.1006/jsbi.2000.4216. 引文格式1維護:顯式使用等標籤 (link)
Mounkes LC, Burke B, Stewart CL. The A-type lamins: nuclear structural proteins as a focus for muscular dystrophy and cardiovascular diseases. Trends Cardiovasc. Med. 2001, 11 (7): 280–5. PMID 11709282. doi:10.1016/S1050-1738(01)00126-8.
Vigouroux C, Magré J, Desbois-Mouthon C; et al. [Major insulin resistance syndromes: clinical and physiopathological aspects]. J. Soc. Biol. 2002, 195 (3): 249–57. PMID 11833462. 引文格式1維護:顯式使用等標籤 (link)
Helbling-Leclerc A, Bonne G, Schwartz K. Emery-Dreifuss muscular dystrophy. Eur. J. Hum. Genet. 2002, 10 (3): 157–61. PMID 11973618. doi:10.1038/sj.ejhg.5200744.
Burke B, Stewart CL. Life at the edge: the nuclear envelope and human disease. Nat. Rev. Mol. Cell Biol. 2002, 3 (8): 575–85. PMID 12154369. doi:10.1038/nrm879.
Novelli G, D'Apice MR. The strange case of the "lumper" lamin A/C gene and human premature ageing. Trends in molecular medicine. 2004, 9 (9): 370–5. PMID 13129702. doi:10.1016/S1471-4914(03)00162-X.
Pasotti M, Repetto A, Pisani A, Arbustini E. [Diseases associated with lamin A/C gene defects: what the clinical cardiologist ought to know]. Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology. 2004, 5 (2): 98–111. PMID 15080529.
Garg A, Cogulu O, Ozkinay F; et al. A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia. J. Clin. Endocrinol. Metab. 2005, 90 (9): 5259–64. PMID 15998779. doi:10.1210/jc.2004-2560. 引文格式1維護:顯式使用等標籤 (link)
Lees-Miller SP. Dysfunction of lamin A triggers a DNA damage response and cellular senescence. DNA Repair (Amst.). 2006, 5 (2): 286–9. PMID 16344005. doi:10.1016/j.dnarep.2005.10.007.
Donadille B, Lascols O, Capeau J, Vigouroux C. Etiological investigations in apparent type 2 diabetes: when to search for lamin A/C mutations?. Diabetes Metab. 2006, 31 (6): 527–32. PMID 16357800. doi:10.1016/S1262-3636(07)70227-6.
Young SG, Meta M, Yang SH, Fong LG. Prelamin A farnesylation and progeroid syndromes. J. Biol. Chem. 2007, 281 (52): 39741–5. PMID 17090536. doi:10.1074/jbc.R600033200.
Sliwińska MA. [The role of lamins and mutations of LMNA gene in physiological and premature aging]. Postepy Biochem. 2007, 53 (1): 46–52. PMID 17718387.