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Mol Biol Cell
2000 Dec 01;1112:4323-37. doi: 10.1091/mbc.11.12.4323.
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Head and/or CaaX domain deletions of lamin proteins disrupt preformed lamin A and C but not lamin B structure in mammalian cells.
Izumi M
,
Vaughan OA
,
Hutchison CJ
,
Gilbert DM
.
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The nuclear lamina is an important determinant of nuclear architecture. Mutations in A-type but not B-type lamins cause a range of human genetic disorders, including muscular dystrophy. Dominant mutations in nuclear lamin proteins have been shown to disrupt a preformed lamina structure in Xenopus egg extracts. Here, a series of deletion mutations in lamins A and B1 were evaluated for their ability to disrupt lamina structure in Chinese hamster ovary cells. Deletions of either the lamin A "head" domain or the C-terminal CaaX domain formed intranuclear aggregates and resulted in the disruption of endogenous lamins A/C but not lamins B1/B2. By contrast, "head-less" lamin B1 localized to the nuclear rim with no detectable effect on endogenous lamins, whereas lamin B1 CaaX domain deletions formed intranuclear aggregates, disrupting endogenous lamins A/C but not lamins B1/B2. Filter binding assays revealed that a head/CaaX domain lamin B1 mutant interacted much more strongly with lamins A/C than with lamins B1/B2. Regulated induction of this mutant in stable cell lines resulted in the rapid elimination of all detectable lamin A protein, whereas lamin C was trapped in a soluble form within the intranuclear aggregates. In contrast to results in Xenopus egg extracts, dominant negative lamin B1 (but not lamin A) mutants trapped replication proteins involved in both the initiation and elongation phases of replication but did not effect cellular growth rates or the assembly of active replication centers. We conclude that elimination of the CaaX domain in lamin B1 and elimination of either the CaaX or head domain in lamin A constitute dominant mutations that can disrupt A-type but not B-type lamins, highlighting important differences in the way that A- and B-type lamins are integrated into the lamina.
Aebi,
The nuclear lamina is a meshwork of intermediate-type filaments.
, Pubmed,
Xenbase
Aebi,
The nuclear lamina is a meshwork of intermediate-type filaments.
,
Pubmed
,
Xenbase
Beck,
Isoprenylation is required for the processing of the lamin A precursor.
1990,
Pubmed
Bravo,
Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites.
1987,
Pubmed
Bridger,
Internal lamin structures within G1 nuclei of human dermal fibroblasts.
1993,
Pubmed
Broers,
Dynamics of the nuclear lamina as monitored by GFP-tagged A-type lamins.
1999,
Pubmed
Chan,
The genetic basis of Weber-Cockayne epidermolysis bullosa simplex.
1993,
Pubmed
Chelsky,
Cell cycle-dependent methyl esterification of lamin B.
1987,
Pubmed
Chipev,
Preferential sites in keratin 10 that are mutated in epidermolytic hyperkeratosis.
1994,
Pubmed
Dechat,
Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins.
2000,
Pubmed
Dimitrova,
Mcm2, but not RPA, is a component of the mammalian early G1-phase prereplication complex.
1999,
Pubmed
,
Xenbase
Dimitrova,
Stability and nuclear distribution of mammalian replication protein A heterotrimeric complex.
2000,
Pubmed
Dimitrova,
The spatial position and replication timing of chromosomal domains are both established in early G1 phase.
1999,
Pubmed
,
Xenbase
Dyer,
Investigations of the pathway of incorporation and function of lamin A in the nuclear lamina.
1999,
Pubmed
,
Xenbase
Dyer,
Cell cycle changes in A-type lamin associations detected in human dermal fibroblasts using monoclonal antibodies.
1997,
Pubmed
Ellis,
GST-lamin fusion proteins act as dominant negative mutants in Xenopus egg extract and reveal the function of the lamina in DNA replication.
1997,
Pubmed
,
Xenbase
Fairley,
The Emery-Dreifuss muscular dystrophy phenotype arises from aberrant targeting and binding of emerin at the inner nuclear membrane.
1999,
Pubmed
Firmbach-Kraft,
The role of CaaX-dependent modifications in membrane association of Xenopus nuclear lamin B3 during meiosis and the fate of B3 in transfected mitotic cells.
1993,
Pubmed
,
Xenbase
Fisher,
cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.
1986,
Pubmed
Flier,
Pushing the envelope on lipodystrophy.
2000,
Pubmed
Foisner,
Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation.
1993,
Pubmed
Furukawa,
The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain.
1998,
Pubmed
Furukawa,
Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin.
1998,
Pubmed
Gerace,
The nuclear envelope lamina is reversibly depolymerized during mitosis.
1980,
Pubmed
Goldberg,
High resolution scanning electron microscopy of the nuclear envelope: demonstration of a new, regular, fibrous lattice attached to the baskets of the nucleoplasmic face of the nuclear pores.
1992,
Pubmed
,
Xenbase
Goldman,
Pathway of incorporation of microinjected lamin A into the nuclear envelope.
1992,
Pubmed
Hamlin,
Defining origins of replication in mammalian cells.
1994,
Pubmed
Heald,
Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis.
1990,
Pubmed
Heitlinger,
The role of the head and tail domain in lamin structure and assembly: analysis of bacterially expressed chicken lamin A and truncated B2 lamins.
1992,
Pubmed
Hennekes,
The role of isoprenylation in membrane attachment of nuclear lamins. A single point mutation prevents proteolytic cleavage of the lamin A precursor and confers membrane binding properties.
1994,
Pubmed
Holtz,
The CaaX motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope.
1989,
Pubmed
Izumi,
Homogeneous tetracycline-regulatable gene expression in mammalian fibroblasts.
1999,
Pubmed
Jenkins,
Nuclei that lack a lamina accumulate karyophilic proteins and assemble a nuclear matrix.
1993,
Pubmed
,
Xenbase
Kitten,
The CaaX motif is required for isoprenylation, carboxyl methylation, and nuclear membrane association of lamin B2.
1991,
Pubmed
Krohne,
The conserved carboxy-terminal cysteine of nuclear lamins is essential for lamin association with the nuclear envelope.
1989,
Pubmed
,
Xenbase
Lehner,
Differential expression of nuclear lamin proteins during chicken development.
1987,
Pubmed
,
Xenbase
Lutz,
Nucleoplasmic localization of prelamin A: implications for prenylation-dependent lamin A assembly into the nuclear lamina.
1992,
Pubmed
McKeon,
Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins.
,
Pubmed
Meier,
The role of lamin LIII in nuclear assembly and DNA replication, in cell-free extracts of Xenopus eggs.
1991,
Pubmed
,
Xenbase
Mical,
The role of sequences unique to nuclear intermediate filaments in the targeting and assembly of human lamin B: evidence for lack of interaction of lamin B with its putative receptor.
1998,
Pubmed
Moir,
Expression in Escherichia coli of human lamins A and C: influence of head and tail domains on assembly properties and paracrystal formation.
1991,
Pubmed
Moir,
Disruption of nuclear lamin organization blocks the elongation phase of DNA replication.
2000,
Pubmed
,
Xenbase
Moir,
Dynamic properties of nuclear lamins: lamin B is associated with sites of DNA replication.
1994,
Pubmed
Morris,
Heart to heart: from nuclear proteins to Emery-Dreifuss muscular dystrophy.
1999,
Pubmed
Newport,
A lamin-independent pathway for nuclear envelope assembly.
1990,
Pubmed
,
Xenbase
Nigg,
Targeting lamin proteins to the nuclear envelope: the role of CaaX box modifications.
1992,
Pubmed
Peter,
In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase.
1990,
Pubmed
Pugh,
Distinct nuclear assembly pathways for lamins A and C lead to their increase during quiescence in Swiss 3T3 cells.
1997,
Pubmed
Quinlan,
Intermediate filament proteins.
1995,
Pubmed
Röber,
Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study.
1989,
Pubmed
Rugg,
Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function.
1993,
Pubmed
Schmidt,
Properties of fluorescently labeled Xenopus lamin A in vivo.
1994,
Pubmed
,
Xenbase
Senior,
Integral membrane proteins specific to the inner nuclear membrane and associated with the nuclear lamina.
1988,
Pubmed
Shackleton,
LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.
2000,
Pubmed
Smythe,
Incorporation of the nuclear pore basket protein nup153 into nuclear pore structures is dependent upon lamina assembly: evidence from cell-free extracts of Xenopus eggs.
2000,
Pubmed
,
Xenbase
Spann,
Disruption of nuclear lamin organization alters the distribution of replication factors and inhibits DNA synthesis.
1997,
Pubmed
,
Xenbase
Sullivan,
Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy.
1999,
Pubmed
Vorburger,
A second higher vertebrate B-type lamin. cDNA sequence determination and in vitro processing of chicken lamin B2.
1989,
Pubmed
Vorburger,
Modification of nuclear lamin proteins by a mevalonic acid derivative occurs in reticulocyte lysates and requires the cysteine residue of the C-terminal CXXM motif.
1989,
Pubmed
Walter,
Regulated chromosomal DNA replication in the absence of a nucleus.
1998,
Pubmed
,
Xenbase
Ward,
Identification of cell cycle-regulated phosphorylation sites on nuclear lamin C.
1990,
Pubmed
,
Xenbase
Weber,
Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina.
1989,
Pubmed
Wolda,
Evidence for modification of lamin B by a product of mevalonic acid.
1988,
Pubmed
Wolin,
A new lamin in Xenopus somatic tissues displays strong homology to human lamin A.
1987,
Pubmed
,
Xenbase
Yang,
Lamin-binding fragment of LAP2 inhibits increase in nuclear volume during the cell cycle and progression into S phase.
1997,
Pubmed
Zhang,
Nuclear lamina and nuclear matrix organization in sperm pronuclei assembled in Xenopus egg extract.
1996,
Pubmed
,
Xenbase
