Nuclear lamins

NA isolation and molecular characterization will be important to define the origin and functions of these proteins. At this time, infected cell nuclei offer the only source of these proteins, and NA have proved resistant to classic nuclear extraction methods (Yao and Jasmer, 1998). NA can be solubilized under conditions that co-extract nuclear lamins a/c and b (4 M urea, pH 8.0). Despite these similar physical properties, NA do not co-localize with lamins in the nucleoskeleton. However, both disulphide bonds and ionic interactions appear to contribute to nuclear complexes containing NA. In addition, NA can be cross-linked within host nuclei with protein cross-linking reagents. The foregoing properties represent current information available for the development of strategies to isolate and characterize these proteins and to investigate host proteins with which NA interact. 

Not all neurons have NFs. Indeed, one entire phylum in the animal kingdom, arthropods, expresses only type V nuclear lamins so arthropod cells have no IF cytoskeletal structures at all. In addition, mature oligodendrocytes lack IFs although their embryonic precursors contain vimentin. Clearly, the IFs are not essential for cell survival. Yet, in large myelinated fibers, NFs make up the bulk of axonal volume and represent a substantial fraction of the total protein in brain. In most organisms, IFs in both glia... 

Caspase-mediated cleavage of specific substrates can explain several of the characteristic features of apoptosis. For example, cleavage of the nuclear lamins and cytoplasmic proteins such as fodrin and gelsolin are required for nuclear and cellular... 

Nuclear lamin proteins and the Ras proteins were later shown to be modified by this prenylation reaction [4-6]. The prenyl molecule involved was foimd to be a 15-carbon farnesyl moiety attached to a C-terminal cysteine by a thioether bond [5,6]. Since these farnesylated targets were involved in cell division and signal transduction associated with cell proliferation, the findings suggested an important role for this pathway in tumor cell... 

Several farnesylated nuclear proteins have been identified. The nuclear lamins A, B, and C function in the assembly and reorganization of the nu-... 

Fisher, D. Z., Chaudhary, N., and Blobel, G. (1986). cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. Proc. Natl. Acad. Sci. USA 83, 6450-6454. 

Hennekes, H., and Nigg, E. A. (1994). 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./ Cell Sci. 107, 1019-1029. 

Fig. 1. Diagram of intermediate filaments (IFs) and their associated proteins. Various IFs on the left are color- and shape-coded and matched with interacting partners on the right. For interactions of nuclear lamins with their associated proteins refer to (Zastrow et al., 2004). This figure is not meant to be comprehensive but is rather a summary of those interactions highlighted in this review.

There is much more to this functional complexity than we have been able to discuss in this review. For instance, we have not touched on the complex intranuclear network mediated by the nuclear lamins, which is critically important for human health as reflected in the numerous disease phenotypes that are emerging due to mutation in lamins and their associated protein partners. We have also not discussed the association of IFs with molecules involved in bacterial and viral pathogenesis, such as the Ebstein-Barr virus latent infection membrane protein (LMP) (Liebowitz et al., 1987) or viral kinases such as the herpes simplex virus US3 kinase (Murata et at, 2002) that may be important in remodeling IFs during infection. It is clear, however, from the many critical cellular functions we have discussed in this review, that the IF structural and signaling scaffold is involved in wide-ranging functions that are important for fundamental... 

Cartaud, A., Ludosky, M. A., Courvalin, J. C., and Cartaud, J. (1990). A protein antigenically related to nuclear lamin B mediates the association of intermediate filaments with desmosomes./. Biol. Chem. Ill, 581-588. 

Herrmann, H., and Foisner, R. (2003). Intermediate filaments Novel assembly models and exciting new functions for nuclear lamins. Cell Mol. Life Sci. 60, 1607-1612. 

Nuclear lamins Three major Mr = 65,000 to 70,000 Nuclear lamina of eukaryotic cells... 

Stuurman N, Sasse B, Fisher PA. 1996. Intermediate filament protein polymerization Molecular analysis of Drosophila nuclear lamin head-to-tail binding. J Struct Biol 117 1-15. 

In addition to yeast a-factor and Ras proteins, the mammalian nuclear lamins were among the first proteins shown to undergo prenylation [100,101]. Lamins are nuclear intermediate filament proteins that dimerize... 

Moir, R., Spann, T., Herrmann, H. and Goldman, R. (2000) Dismption of nuclear lamin organization blocks the elongation phase of DNA replication. J. Cell Biol. 149, 1179—1192. 

Spann, TR, Moir, R.D., Goldman, A.E., Stick, R. and Goldman, R.D. (1997) Dismption of nuclear lamin organization alters the distribution of replication factors and inhibits DNA synthesis. J. Cell Biol. 136, 1201-1212. 

Stuurman, N., Heins, S. and Aebi, U. (1998) Nuclear lamins their structure, assembly, and interactions. J. Struct. Biol. 122, 42-66. 

Ye, Q., Barton, R.M. and Worman, H.J. (1998) Nuclear lamin-binding proteins. Subcell. Biochem. 31, 587-610. 

The increase in nuclear cyclin B/CDKl activity promotes phosphorylation of nuclear substrates that are necessary for mitosis, such as nuclear envelope breakdown, spindle formation, chromatin condensation, and restmcturing of the Golgi and endoplasmic reticulum (85, 86). Numerous cyclin B/CDKl substrates have been dehned, which include nuclear lamins, nucleolar proteins, centrosomal proteins, components of the nuclear pore complex, and microtubule-associated proteins (87-89). Cyclin B/CDKl complexes also phosphorylate MCM4 to block replication of DNA, the TFIIH subunit of RNA polymerase II to inhibit transcription, and the ribosomal S6 protein kinase to prevent translation during mitosis (90-92). 

The carboxyl terminal four amino acids constitute a CAAX sequence (where A is any aliphatic amino acid and X is any amino acid) that is highly conserved among all ras and ras-related genes. This sequence is present not only in ras and related proteins but also in the carboxyl terminus of other proteins, including the o and Y-subunits of several heterotrimeric G-proteins, nuclear lamins and unprocessed yeast alpha mating factor. This motif has been shown to be responsible for carboxyl terminal modification via isoprenylation for attachment of ras (and other proteins) to the irmer leaflet of the plasma membrane (Bimbaumer, Bimbaumer, 1995 Khosravi-Far, Der, 1994). 

In most cells the intermediate filaments provide the scaffolding for the cytoskeleton They may account for only 1% of the protein in a cell but provide up to 85% of the protein in the tough outer layers of skin. Intermediate filament proteins are encoded by over 50 human genes which specify proteins of various sizes, structures, and properties. However, all of them have central 300- to 330-residue a-helical regions through which the molecules associate in parallel pairs to form coiled-coil rods with globular domains at the ends (Fig. 7-31). Some of these proteins, such as the keratin of skin, are insoluble. Others, including the nuclear lamins (Chapter 27) and vimentin, dissociate and reform filaments reversibly. 

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