The Nuclear Matrix

The interphase nucleus is thought to contain a 3-dimensional filamentous protein network referred to as nuclear matrix (also: scaffold, skeleton). It provides a framework to maintain the overall size and shape of the nucleus. The matrix acts as a structural attachment site for the DNA loops during the interphase: evolutionary highly conserved 300-1000 bp long DNA sequences, referred to as SARs (Scaffold Associated Regions), have been identified that define the base of DNA loops, anchoring them to specific proteins. By means of such chromosomal attachment sites, the matrix might help to organize chromosomes, localize genes, and regulate DNA transcription and replication within the nucleus.

Cleavage of Nuclear Matrix Proteins during Apoptosis

The role and fate of nuclear matrix proteins during the process of apoptosis have not yet been comprehensively investigated. In the early phase of apoptosis, as during chromatin condensation, the nuclear envelop has been found to remain morphologically intact, while the underlying lamina disappears. Caspase-6 is supposed to be the major laminase (cleaving lamin A) in cells undergoing apoptosis, though there might be another laminase for B type lamins. Other nuclear proteins that undergo proteolysis are the abundand matrix components Topoisomerase II alpha and poly(ADP-ribose)polymerase (PARP). PARP is possibly the best characterized proteolytic substrate of caspases, being cleaved during the execution phase of apoptosis, probably primarily by Caspase-3 and Caspase-7. Moreover, the 70 kDa protein component of the U1 snRNP (U1-70 kDa) is cleaved during apoptosis (probably by Caspase-3 and Caspase-7) what may have a dominant-negative effect on splicing. The Nuclear Mitotic associated protein (NuMA) is also proteolytic degraded during apoptosis and is a component of the fibrogranular nuclear bodies (fgNB).

Other changes in the Nuclear Matrix during Apoptosis

By two-dimensional electrophoresis the status of nulear matrix associated proteins was examined (Gerner et al., 1998, Exp. Cell. Res., 238: 472-480). This study revealed that the majority of those proteins are maintained during the progress of apoptosis. Though cell morphology already changed markedly 1h after apoptosis induction, the pattern of nuclear matrix proteins was not significantly affected at the same time: thus, the early apoptotic events of cell shrinkage and cytoplasmic compaction were not accompanied by detectable changes in nuclear matrix protein composition. Later in the course of apoptosis, some new nuclear matrix protein spots appeared on the 2D-gels, and the intensities of some preexisting spots increased. One of those spots may be identical with heat shock protein hsp27. Other spots may result from proteolytically degraded protein-fragments formed by activated caspases, by association of nuclear factors to the matrix, or translocation of specific cytoplasmic proteins to nuclear sites.
Another morphological feature of nuclear apoptosis might be the formation of so called fibrogranular nuclear bodies (fbNBs) that originate from the nucleolus (Zweyer et al., 1997, Exp. Cell Res, 230:325-336). The fbNBs contain several nuclear matrix proteins: the nucleoskeleton proteins p125 and p160, PCNA, NuMA, the Scaffold Associated Region (SAR) binding polypeptide SATB1, and a number of proteins related to RNA metabolism, for example a 105 kDa constituent of the nuclear spliceosome and SAF-A/hnRNP-U, another polypeptide that binds to SARs. Among those fgNB associated proteins only NuMA is proteolytical degraded. The fbNBs appeared in a number of different systems underging apoptosis, even in the absence of internucleosomal cleavage.


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