Proteins that associate with lamins: Many faces, many functions

Schirmer, Eric C.; Foisner, Roland

doi:10.1016/j.yexcr.2007.03.012

Cited by 152 publications

(123 citation statements)

References 148 publications

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“…Two proteins, Emerin and Man1, have been shown to play an important role in the tethering of repressed genes to the nuclear periphery (Liu et al 2003). Both proteins have a LEM domain that recruits autointegration factor (BAF), which associates with transcription repressors, such as Crx1 (for review, see Schirmer and Foisner 2007). In addition, Man1 can interact with Smads and ␤-catenin, antagonizing signaling by TGF␤ and Wnt proteins, respectively (Pan et al 2005;Markiewicz et al 2006).…”

Section: Association Of Genes With the Nuclear Periphery And Nuclear mentioning

confidence: 99%

“…Moreover, the lamin B receptor (LBR) has been implicated in heterochromatin regulation via interaction with HP1, which binds to histone H3K9-trimethyl marks (Makatsori et al 2001;Polioudaki et al 2001). Finally, the SUN-Nesprin complex links the perinuclear skeleton with the cytoplasmic filament system (for detailed review, see Schirmer and Foisner 2007).…”

Section: Association Of Genes With the Nuclear Periphery And Nuclear mentioning

confidence: 99%

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Dynamics and interplay of nuclear architecture, genome organization, and gene expression

Schneider¹,

Grosschedl²

2007

Genes Dev.

367

313

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The organization of the genome in the nucleus of a eukaryotic cell is fairly complex and dynamic. Various features of the nuclear architecture, including compartmentalization of molecular machines and the spatial arrangement of genomic sequences, help to carry out and regulate nuclear processes, such as DNA replication, DNA repair, gene transcription, RNA processing, and mRNA transport. Compartmentalized multiprotein complexes undergo extensive modifications or exchange of protein subunits, allowing for an exquisite dynamics of structural components and functional processes of the nucleus. The architecture of the interphase nucleus is linked to the spatial arrangement of genes and gene clusters, the structure of chromatin, and the accessibility of regulatory DNA elements. In this review, we discuss recent studies that have provided exciting insight into the interplay between nuclear architecture, genome organization, and gene expression.

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Section: Association Of Genes With the Nuclear Periphery And Nuclear mentioning

confidence: 99%

Section: Association Of Genes With the Nuclear Periphery And Nuclear mentioning

confidence: 99%

Dynamics and interplay of nuclear architecture, genome organization, and gene expression

Schneider¹,

Grosschedl²

2007

Genes Dev.

367

313

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“…The outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum (ER) and connects with the inner nuclear membrane (INM) at the nuclear pore membrane (POM; Lusk et al, 2007). Integral membrane proteins that reside in the INM are initially inserted into the endoplasmic reticulum (ER) membrane and move via the POM to the INM where they maintain a concentrated localization by binding to chromatin or tethering to the nuclear lamina (Powell and Burke, 1990;Soullam and Worman, 1993;Holmer and Worman, 2001;Ohba et al, 2004;Lusk et al, 2007;Schirmer and Foisner, 2007). Until recently, conventional wisdom held that the localization of proteins to either the ER membrane or the INM is mutually exclusive.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Prelamin A Biogenesis Reveals the Nucleus to be a CaaX Processing Compartment

Barrowman¹,

Hamblet²,

George³

et al. 2008

MBoC

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Proteins establish and maintain a distinct intracellular localization by means of targeting, retention, and retrieval signals, ensuring most proteins reside predominantly in one cellular location. The enzymes involved in the maturation of lamin A present a challenge to this paradigm. Lamin A is first synthesized as a 74-kDa precursor, prelamin A, with a C-terminal CaaX motif and undergoes a series of posttranslational modifications including CaaX processing (farnesylation, aaX cleavage and carboxylmethylation), followed by endoproteolytic cleavage by Zmpste24. Failure to cleave prelamin A results in progeria and related premature aging disorders. Evidence suggests prelamin A is imported directly into the nucleus where it is processed. Paradoxically, the processing enzymes have been shown to reside in the cytosol (farnesyltransferase), or are ER membrane proteins (Zmpste24, Rce1, and Icmt) with their active sites facing the cytosol. Here we have reexamined the cellular site of prelamin A processing, and show that the mammalian and yeast processing enzymes Zmpste24 and Icmt exhibit a dual localization to the inner nuclear membrane, as well as the ER membrane. Our findings reveal the nucleus to be a physiologically relevant location for CaaX processing, and provide insight into the biology of a protein at the center of devastating progeroid diseases. INTRODUCTIONThe nuclear envelope consists of an inner and outer membrane. The outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum (ER) and connects with the inner nuclear membrane (INM) at the nuclear pore membrane (POM; Lusk et al., 2007). Integral membrane proteins that reside in the INM are initially inserted into the endoplasmic reticulum (ER) membrane and move via the POM to the INM where they maintain a concentrated localization by binding to chromatin or tethering to the nuclear lamina (Powell and Burke, 1990;Soullam and Worman, 1993;Holmer and Worman, 2001;Ohba et al., 2004;Lusk et al., 2007;Schirmer and Foisner, 2007). Until recently, conventional wisdom held that the localization of proteins to either the ER membrane or the INM is mutually exclusive. For example, proteins that are found within the INM, such as LAP1, are not generally found throughout the ER/ONM; likewise, ER proteins such as HMG-CoA reductase are strictly localized to the ER (Wright et al., 1988;Powell and Burke, 1990;Deng and Hochstrasser, 2006). It was recently shown that a notable exception to this paradigm is the yeast E3 ubiquitin ligase, Doa10p. Doa10p was long known to reside in the ER membrane (Swanson et al., 2001;Kreft et al., 2006). However, recent data indicate that Doa10p exhibits dual steady-state localizations, residing and functioning in both the ER membrane where it mediates ER-associated degradation of membrane and secretory proteins, and in the INM where it mediates degradation of the nuclear transcription factor MAT␣2 (Deng and Hochstrasser, 2006).The present study documents another exception to the mutual exclusivity of ER membrane and INM localizati...

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“…T he nuclear lamina, an intermediate filament meshwork located adjacent to the inner nuclear membrane, provides scaffolding for the cell nucleus and plays a role in many vital processes in the cell, including the regulation of gene expression and chromatin structure (1,2). The nuclear lamina is composed primarily of four lamin proteins: lamins A, B1, B2, and C (3).…”

mentioning

confidence: 99%

Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA

Jung¹,

Coffinier²,

Choe

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

190

217

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Lamins A and C, alternatively spliced products of the LMNA gene, are key components of the nuclear lamina. The two isoforms are found in similar amounts in most tissues, but we observed an unexpected pattern of expression in the brain. Western blot and immunohistochemistry studies showed that lamin C is abundant in the mouse brain, whereas lamin A and its precursor prelamin A are restricted to endothelial cells and meningeal cells and are absent in neurons and glia. Prelamin A transcript levels were low in the brain, but this finding could not be explained by alternative splicing. In lamin Aonly knockin mice, where alternative splicing is absent and all the output of the gene is channeled into prelamin A transcripts, large amounts of lamin A were found in peripheral tissues, but there was very little lamin A in the brain. Also, in knockin mice expressing exclusively progerin (a toxic form of prelamin A found in Hutchinson-Gilford progeria syndrome), the levels of progerin in the brain were extremely low. Further studies showed that prelamin A expression, but not lamin C expression, is down-regulated by a brain-specific microRNA, miR-9. Expression of miR-9 in cultured cells reduced lamin A expression, and this effect was abolished when the miR-9-binding site in the prelamin A 3′ UTR was mutated. The down-regulation of prelamin A expression in the brain could explain why mouse models of Hutchinson-Gilford progeria syndrome are free of central nervous system pathology.

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Proteins that associate with lamins: Many faces, many functions

Cited by 152 publications

References 148 publications

Dynamics and interplay of nuclear architecture, genome organization, and gene expression

Dynamics and interplay of nuclear architecture, genome organization, and gene expression

Analysis of Prelamin A Biogenesis Reveals the Nucleus to be a CaaX Processing Compartment

Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA

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