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Nuclear lamins: key regulators of nuclear structure and activities.

Prokocimer M, Davidovich M, Nissim-Rafinia M, Wiesel-Motiuk N, Bar DZ, Barkan R, Meshorer E, Gruenbaum Y - J. Cell. Mol. Med. (2009)

Bottom Line: A fraction of lamins is also present in the nucleoplasm, where it forms stable complexes and is associated with specific nucleoplasmic proteins.The lamins and their associated proteins are required for most nuclear activities, mitosis and for linking the nucleoplasm to all major cytoskeletal networks in the cytoplasm.Mutations in nuclear lamins and their associated proteins cause about 20 different diseases that are collectively called laminopathies'.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Israel.

ABSTRACT
The nuclear lamina is a proteinaceous structure located underneath the inner nuclear membrane (INM), where it associates with the peripheral chromatin. It contains lamins and lamin-associated proteins, including many integral proteins of the INM, chromatin modifying proteins, transcriptional repressors and structural proteins. A fraction of lamins is also present in the nucleoplasm, where it forms stable complexes and is associated with specific nucleoplasmic proteins. The lamins and their associated proteins are required for most nuclear activities, mitosis and for linking the nucleoplasm to all major cytoskeletal networks in the cytoplasm. Mutations in nuclear lamins and their associated proteins cause about 20 different diseases that are collectively called laminopathies'. This review concentrates mainly on lamins, their structure and their roles in DNA replication, chromatin organization, adult stem cell differentiation, aging, tumorogenesis and the lamin mutations leading to laminopathic diseases.

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Prelamin A processing. Premature lamin A is going through four processing steps until it becomes a mature lamin A, including farnesylation of the cysteine at the carboxy terminus, cleavage of the three carboxy-terminal amino acids (aaX) by either ZMPSTE24 or RceI, carboxymethylation of the farnesylated cysteine by isoprenylcysteine methyltransferase and cleavage of the 15 terminal amino acids, including the farnesylated and carboxymethylated cysteine, by ZMPSTE24.
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fig02: Prelamin A processing. Premature lamin A is going through four processing steps until it becomes a mature lamin A, including farnesylation of the cysteine at the carboxy terminus, cleavage of the three carboxy-terminal amino acids (aaX) by either ZMPSTE24 or RceI, carboxymethylation of the farnesylated cysteine by isoprenylcysteine methyltransferase and cleavage of the 15 terminal amino acids, including the farnesylated and carboxymethylated cysteine, by ZMPSTE24.

Mentions: Lamins are type V intermediate filaments (IFs) and like all members of the IF family of proteins, they have the tripartite domain organization of a central α helical rod domain, flanked by a short head and a longer tail domains (Fig. 1A). The rod domain is made of four coiled-coil segments: 1A, 1B, 2A and 2B, each of which is made of heptad repeats. The coiled-coil segments are linked by three linkers termed L1, L12 and L2, which are conserved in length and sequence among lamins [1, 2]. The end segments of the central rod domain (∼30 amino acids on both sides) are similar among lamins, as well as in all IF proteins. When mutated or deleted, they affect the assembly of dimers into higher-order structures [1]. Coil 1B in all lamins is similar to invertebrate cytoplasmic IFs and is 42 amino acids (6 heptads) longer than vertebrate cytoplasmic IFs [2]. The lamin tail domain contains a ∼120-residue immunoglobulin (Ig) fold [3]. Between the rod domain and the Ig fold there is an unfolded region containing a nuclear localization signal (NLS). The carboxy tail domain of all B-type lamins and lamin A (but not lamin C) proteins contains a CAAX motif, which undergoes post-translational modifications (see below, Fig. 2).


Nuclear lamins: key regulators of nuclear structure and activities.

Prokocimer M, Davidovich M, Nissim-Rafinia M, Wiesel-Motiuk N, Bar DZ, Barkan R, Meshorer E, Gruenbaum Y - J. Cell. Mol. Med. (2009)

Prelamin A processing. Premature lamin A is going through four processing steps until it becomes a mature lamin A, including farnesylation of the cysteine at the carboxy terminus, cleavage of the three carboxy-terminal amino acids (aaX) by either ZMPSTE24 or RceI, carboxymethylation of the farnesylated cysteine by isoprenylcysteine methyltransferase and cleavage of the 15 terminal amino acids, including the farnesylated and carboxymethylated cysteine, by ZMPSTE24.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496104&req=5

fig02: Prelamin A processing. Premature lamin A is going through four processing steps until it becomes a mature lamin A, including farnesylation of the cysteine at the carboxy terminus, cleavage of the three carboxy-terminal amino acids (aaX) by either ZMPSTE24 or RceI, carboxymethylation of the farnesylated cysteine by isoprenylcysteine methyltransferase and cleavage of the 15 terminal amino acids, including the farnesylated and carboxymethylated cysteine, by ZMPSTE24.
Mentions: Lamins are type V intermediate filaments (IFs) and like all members of the IF family of proteins, they have the tripartite domain organization of a central α helical rod domain, flanked by a short head and a longer tail domains (Fig. 1A). The rod domain is made of four coiled-coil segments: 1A, 1B, 2A and 2B, each of which is made of heptad repeats. The coiled-coil segments are linked by three linkers termed L1, L12 and L2, which are conserved in length and sequence among lamins [1, 2]. The end segments of the central rod domain (∼30 amino acids on both sides) are similar among lamins, as well as in all IF proteins. When mutated or deleted, they affect the assembly of dimers into higher-order structures [1]. Coil 1B in all lamins is similar to invertebrate cytoplasmic IFs and is 42 amino acids (6 heptads) longer than vertebrate cytoplasmic IFs [2]. The lamin tail domain contains a ∼120-residue immunoglobulin (Ig) fold [3]. Between the rod domain and the Ig fold there is an unfolded region containing a nuclear localization signal (NLS). The carboxy tail domain of all B-type lamins and lamin A (but not lamin C) proteins contains a CAAX motif, which undergoes post-translational modifications (see below, Fig. 2).

Bottom Line: A fraction of lamins is also present in the nucleoplasm, where it forms stable complexes and is associated with specific nucleoplasmic proteins.The lamins and their associated proteins are required for most nuclear activities, mitosis and for linking the nucleoplasm to all major cytoskeletal networks in the cytoplasm.Mutations in nuclear lamins and their associated proteins cause about 20 different diseases that are collectively called laminopathies'.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Israel.

ABSTRACT
The nuclear lamina is a proteinaceous structure located underneath the inner nuclear membrane (INM), where it associates with the peripheral chromatin. It contains lamins and lamin-associated proteins, including many integral proteins of the INM, chromatin modifying proteins, transcriptional repressors and structural proteins. A fraction of lamins is also present in the nucleoplasm, where it forms stable complexes and is associated with specific nucleoplasmic proteins. The lamins and their associated proteins are required for most nuclear activities, mitosis and for linking the nucleoplasm to all major cytoskeletal networks in the cytoplasm. Mutations in nuclear lamins and their associated proteins cause about 20 different diseases that are collectively called laminopathies'. This review concentrates mainly on lamins, their structure and their roles in DNA replication, chromatin organization, adult stem cell differentiation, aging, tumorogenesis and the lamin mutations leading to laminopathic diseases.

Show MeSH