The characterization and localization of the mouse thymopoietin/lamina-associated polypeptide 2 gene and its alternatively spliced products.

Berger, Raanan; Theodor, Livia; Shoham, Jacob; Gokkel, Ellen; Brok‐Simoni, Frida; Avraham, Karen B.; Copeland, Neal G.; Jenkins, Nancy A.; Rechavi, Gideon; Simon, Amos J.

doi:10.1101/gr.6.5.361

Cited by 119 publications

(95 citation statements)

References 29 publications

(31 reference statements)

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“…Studies with fibroblast cells have revealed that fibroblast to pre-adipocyte transformation is strongly connected to LAP2 , the member of the LAP2 protein family (Dorner et al 2006). While most splice variants associate with the nuclear envelope, LAP2 is involved in several nucleoplasmic activities including cell-cycle control and differentiation (Berger et al 1996;Hutchison et al 2001). LAP2 is synthesized in the cytoplasm and is then transported into the nucleus by a PKC-dependent mechanism (Dreger et al 1999).…”

Section: Trans-differentiation Of Fibroblasts Into Adipocytesmentioning

confidence: 99%

Central Immune Senescence, Reversal Potentials

Kvell

Pongrácz

2012

Senescence

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Section: Trans-differentiation Of Fibroblasts Into Adipocytesmentioning

confidence: 99%

Central Immune Senescence, Reversal Potentials

Kvell

Pongrácz

2012

Senescence

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“…Analysis of LAP2 has shown that at least six separate mRNAs are generated from the gene, two of which lack a membrane-spanning segment [56]. In addition to the NE-bound ß-variant, isotypespecific antibodies exist only for the soluble α-variant, which localizes predominantly in the nucleoplasm (with minimal concentration at the nuclear rim) [49].…”

Section: Numbering the Set Of Ne Proteinsmentioning

confidence: 99%

The nuclear membrane proteome: extending the envelope

Schirmer

Gerace

2005

Trends in Biochemical Sciences

127

109

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The marriage of proteomics with cell biology has produced extensive inventories of the proteins that inhabit several subcellular organelles. Recent proteomic analysis has identified a large number of new putative transmembrane proteins in the nuclear envelope, and transcriptome profiling suggests that the nuclear membrane proteome exhibits some significant variations among different tissues. Cell type-specific differences in the composition of protein subcomplexes of the nuclear envelope, particularly those containing the disease-associated protein lamin A, could yield distinctive functions and so explain the tissue-specificity of a diverse group of nuclear envelope-linked disorders in humans. Considered together, these recent results suggest an unexpected functional complexity at the nuclear envelope.3 An introduction to the nuclear envelopeThe past few years have seen an explosion in the number of identified nuclear envelope (NE) proteins as well as in the number of their associated diseases. The NE (Figure 1), which is continuous with the more peripheral ER, contains an outer (ONM) and inner nuclear membrane (INM) that are joined at the nuclear pore membrane, giving rise to three different subdomains within nuclear membranes. The ONM is functionally similar to the more peripheral ER, but also is thought to contain some distinct resident proteins. The INM contains a large group of distinctive transmembrane proteins and is lined by a polymer of intermediate filament proteins called lamins. As many as four major lamin subtypes (lamin A, C, B1, and B2) are expressed in mammalian cells in a developmentally-regulated manner. Most lamin subtypes can be modified with lipid moieties that facilitate their targeting to the NE, and a fraction of some lamins occurs in the nucleoplasm as well as at the INM (reviewed in [1]). The lamin polymer and interacting proteins at the INM collectively comprise the nuclear lamina. The nuclear pore membrane is closely associated with nuclear pore complexes (NPCs), the main macromolecular transport channels across the NE. The transport functions and proteome of the NPC have been extensively characterized [2,3], and will not be further considered here. It is generally agreed that the lamina has a role in nuclear morphology and stability [4][5][6], and support for a wide and ever-increasing array of additional functions has emerged from recent studies. Lamins and lamina-associated membrane proteins have been linked to activities as diverse as transcription [7][8][9][10], DNA replication [11,12], nuclear anchoring/ migration within the cell [13], and signaling cascades [14]. To what extent these are direct or indirect effects of lamina proteins remains to be elucidated. 4Consistent with the notion that the nuclear lamina is involved in a diverse range of basic cellular functions, at least fifteen inherited diseases and syndromes have been linked to lamins A/C and certain associated NE transmembrane proteins.These include muscular dystrophies, lipodystrophies, neuropathy, cardiomyo...

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“…LAP2 was also first identified by reaction with a monoclonal antibody and shown to be an integral membrane protein that binds to nuclear lamins and chromatin (16). Several isoforms of LAP2, which have also been called thymopoietins because they were thought to possibly be thymocyte growth factors, are generated by alternative RNA splicing (17)(18)(19)(20)(21). Some of the LAP2 isoforms are integral proteins of the inner nuclear membrane, with nucleoplasmic amino-terminal domains and single transmembrane segments, while others are nonmembrane nuclear polypeptides.…”

mentioning

confidence: 99%

MAN1, an Inner Nuclear Membrane Protein That Shares the LEM Domain with Lamina-associated Polypeptide 2 and Emerin

Feng¹,

Blake²,

Callebaut³

et al. 2000

Journal of Biological Chemistry

308

250

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The "MAN antigens" are polypeptides recognized by autoantibodies from a patient with a collagen vascular disease and localized to the nuclear envelope. We now show that one of the human MAN antigens termed MAN1 is a 82.3-kDa protein with an amino-terminal domain followed by two hydrophobic segments and a carboxylterminal tail. The MAN1 gene contains seven proteincoding exons and is assigned to human chromosome 12q14. Its mRNA is approximately 5.5 kilobases and is detected in several different cell types that were examined. Cell extraction experiments show that MAN1 is an integral membrane protein. When expressed in transfected cells, MAN1 is exclusively targeted to the nuclear envelope, consistent with an inner nuclear membrane localization. Protein sequence analysis reveals that MAN1 shares a conserved globular domain of approximately 40 amino acids, which we term the LEM module, with inner nuclear membrane proteins lamina-associated polypeptide 2 and emerin. The LEM module is also present in two proteins of Caenorhabditis elegans. These results show that MAN1 is an integral protein of the inner nuclear membrane that shares the LEM module with other proteins of this subcellular localization.Only a few proteins other than the nuclear lamins, some with various isoforms, have been localized to the inner nuclear membrane during interphase. The first to be identified was avian lamin B receptor (LBR) 1 (1, 2). LBR was subsequently characterized in mammals (3-6), and an immunochemically crossreactive protein has been identified in sea urchins (7). LBR has a nucleoplasmic, amino-terminal domain of approximately 200 amino acids that binds to B-type lamins and chromatin proteins and confers inner nuclear membrane retention (2, 4, 8 -12). The amino-terminal domain of LBR is followed by a hydrophobic domain with eight putative transmembrane segments that is similar in sequence to sterol reductases, including two human proteins of the endoplasmic reticulum, one of which is a 7-dehydrocholesterol reductase (13).Two other integral proteins of the inner nuclear membrane have been termed lamina-associated polypeptides (LAPs). Three related isoforms of rat LAP1 (LAP1A, LAP1B, and LAP1C) were identified by reaction with a single monoclonal antibody and shown to be integral membrane proteins associated with the nuclear lamina (14). LAP1C has a nucleoplasmic amino-terminal domain followed by one transmembrane segment, and the other LAP1 isoforms are probably of similar overall structure, arising from the same gene by alternative RNA splicing (15). LAP2 was also first identified by reaction with a monoclonal antibody and shown to be an integral membrane protein that binds to nuclear lamins and chromatin (16). Several isoforms of LAP2, which have also been called thymopoietins because they were thought to possibly be thymocyte growth factors, are generated by alternative RNA splicing (17-21). Some of the LAP2 isoforms are integral proteins of the inner nuclear membrane, with nucleoplasmic amino-terminal domains and single transmembr...

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The characterization and localization of the mouse thymopoietin/lamina-associated polypeptide 2 gene and its alternatively spliced products.

Cited by 119 publications

References 29 publications

Central Immune Senescence, Reversal Potentials

Central Immune Senescence, Reversal Potentials

The nuclear membrane proteome: extending the envelope

MAN1, an Inner Nuclear Membrane Protein That Shares the LEM Domain with Lamina-associated Polypeptide 2 and Emerin

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