Lamina-associated polypeptide 2α regulates cell cycle progression and differentiation via the retinoblastoma–E2F pathway

Dorner, D.; Vlcek, Sylvia; Foeger, Nicole; Gajewski, Andreas; Makolm, Christian; Gotzmann, Josef; Hutchison, Christopher J.; Foisner, Roland

doi:10.1083/jcb.200511149

Cited by 151 publications

(190 citation statements)

References 55 publications

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“…Finally, LAP2α-lamin A complexes in the nuclear interior bind the tumor supressor retinoblastoma (Rb) [93], which is a negative regulator of E2F-dependent transcription controlling the balance between proliferation and differentiation [94]. Accordingly LAP2 can associate with E2F/Rbresponsive promoters and impair expression of E2F-target genes upon cell cycle exit and differentiation [95].…”

Section: Lap-complexes Function In Gene Expression and Signalingmentioning

confidence: 99%

“…This finding again argues that disease-causing mutations in lamin A and LAP2α impair the functions of the nucleoplasmic complex. Because LAP2α can regulate Rb function during differentiation [95], it was proposed that mutations in LAP2α may affect the differentiation of adult muscle stem cells, which may impair homeostasis and regeneration of heart muscle tissues in patients [106].…”

Section: Impairment Of Lap Functions Gives Rise To Human Diseasesmentioning

confidence: 99%

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Proteins that associate with lamins: Many faces, many functions

Schirmer

Foisner

2007

Experimental Cell Research

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152

119

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Section: Lap-complexes Function In Gene Expression and Signalingmentioning

confidence: 99%

Section: Impairment Of Lap Functions Gives Rise To Human Diseasesmentioning

confidence: 99%

Proteins that associate with lamins: Many faces, many functions

Schirmer

Foisner

2007

Experimental Cell Research

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152

119

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“…The LAP2 exists as six alternatively spliced isoforms, four of which (LAP2-, -, -, and -) interact with LMNB1 and localize to the inner nuclear membrane (Dorner et al, 2006). LAP2- has been implicated in regulating cell proliferation in murine and human cells (Pekovic et al, 2007;Naetar et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Lamin B1 fluctuations have differential effects on cellular proliferation and senescence

Dreesen¹,

Chojnowski²,

Ong³

et al. 2013

J Exp Med

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“…The LAP2␣-lamin A/C-pRb complex is thought to regulate cell proliferation and differentiation in adult stem cells (3,12). During mitosis, LAP2␣ dissociates from chromosomes in a phosphorylation-dependent manner and is redistributed throughout the mitotic cytoplasm, like most nuclear lamina components (14, 15).…”

mentioning

confidence: 99%

“…LAP2␣ is exclusively located in the nucleoplasm in interphase and interacts with lamin A/C (11) and hypophosphorylated retinoblastoma protein (pRb) via distinct C-terminal domains (12,13). The LAP2␣-lamin A/C-pRb complex is thought to regulate cell proliferation and differentiation in adult stem cells (3,12).…”

mentioning

confidence: 99%

Lamina-associated Polypeptide 2-α Forms Homo-trimers via Its C Terminus, and Oligomerization Is Unaffected by a Disease-causing Mutation

Snyers

Vlcek

Dechat

et al. 2007

Journal of Biological Chemistry

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The nucleoplasmic protein, Lamina-associated polypeptide (LAP) 2␣, is one of six alternatively spliced products of the LAP2gene, which share a common N-terminal region. In contrast to the other isoforms, which also share most of their C termini, LAP2␣ has a large unique C-terminal region that contains binding sites for chromatin, A-type lamins, and retinoblastoma protein. By immunoprecipitation analyses of LAP2␣ complexes from cells expressing differently tagged LAP2␣ proteins and fragments, we demonstrate that LAP2␣ forms higher order structures containing multiple LAP2␣ molecules in vivo and that complex formation is mediated by the C terminus. Solid phase binding assays using recombinant and in vitro translated LAP2␣ fragments showed direct interactions of LAP2␣ C termini. Cross-linking of LAP2␣ complexes and multiangle light scattering of purified LAP2␣ revealed the existence of stable homo-trimers in vivo and in vitro. Finally, we show that, in contrast to the LAP2␣-lamin A interaction, its self-association is not affected by a disease-linked single point mutation in the LAP2␣ C terminus.The nuclear envelope comprises the inner and outer nuclear membranes, the nuclear pore complexes, and the nuclear lamina, which underlies the inner nuclear membrane (1, 2). The nuclear lamina is the major structural framework in the nucleus of multicellular eukaryotes and is composed of a filamentous meshwork of type V intermediate filament proteins, the lamins. B-type lamins, encoded by two human genes (LMNB1 and LMNB2), are essential for cell viability. In contrast, the four A-type lamins (A, C, C2, and A⌬10), representing splicing isoforms of the LMNA gene, are dispensable for viability of individual cells but have crucial functions in tissue organization after birth (3, 4).In addition to the lamins, the nuclear lamina contains a number of integral membrane proteins of the inner nuclear membrane, the best characterized of which are the Lamin B receptor, Lamina-associated polypeptide (LAP), 4 and the three LEM domain-containing proteins LAP2␤, emerin and MAN1 (5, 6). All these proteins interact with lamin A/C and/or B and contribute to anchorage of the nuclear membrane to the lamina. The LEM domain, a conserved 40-amino-acid motif located near the N terminus of the LEM family proteins, interacts with the DNA-binding protein barrier-to-autointegration factor (BAF) and mediates the binding of these proteins to chromatin (7). In LAP2 proteins, a LEM-like segment at the very N terminus has been shown to interact with DNA directly (8).The family of LAP2 proteins includes six alternatively spliced isoforms derived from the same gene (9). Most LAP2 isoforms are closely related structurally and functionally and are localized to the inner nuclear membrane, such as LAP2␤. In contrast, LAP2␣ shares only the N-terminal 187 amino acids with the other isoforms, including the LEM and LEM-like domains, but otherwise possesses a unique 506-amino-acid C-terminal region without a transmembrane domain (see Fig. 1A), encoded by one large exon...

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Lamina-associated polypeptide 2α regulates cell cycle progression and differentiation via the retinoblastoma–E2F pathway

Cited by 151 publications

References 55 publications

Proteins that associate with lamins: Many faces, many functions

Proteins that associate with lamins: Many faces, many functions

Lamin B1 fluctuations have differential effects on cellular proliferation and senescence

Lamina-associated Polypeptide 2-α Forms Homo-trimers via Its C Terminus, and Oligomerization Is Unaffected by a Disease-causing Mutation

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