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.
References
bstract
The review summarizes literature data on alterations of structure or expression of different nuclear matrix
proteins in hereditary syndromes. From the point of view of involvement of nuclear matrix proteins in
etiology and pathogenesis of the disease hereditary pathologies can be classified in pathologies with
pathogenesis associated with defects of nuclear matrix proteins and pathologies associated to changes of
the nuclear matrix protein spectrum. The first group includes laminopathies, hereditary diseases with
abnormal nuclear-matrix associated proteins and triplet extension diseases associated with accumulation
of abnormal proteins in the nuclear matrix. Laminopathies are hereditary diseases coupled to structural
defects of the nuclear lamina. These diseases include Emery-Dreifuss muscular dystrophy, limb girdle
muscular dystrophy, dilated cardiomyopathy (DCM) with conduction system disease, familial partial
lipodystrophy (FPLD), autosomal recessive axonal neuropathy (Charcot-Marie-Tooth disorder type 2,
CMT2), mandibuloacral dysplasia (MAD), Hutchison Gilford Progeria syndrome (HGS), Greenberg
Skeletal Dysplasia, and Pelger-Huet anomaly (PHA). Most of them are due to mutations in the lamin A/C
gene, one - to mutations in emerin gene, some are associated with mutations in Lamin B receptor gene.
In Werner's, Bloom's, Cockayne's syndromes, Fanconi anemia, multiple carboxylase deficiency mutations
in nuclear matrix protein or enzyme gene lead to deficient DNA repair, abnormal regulation of cell growth
and differentiation or other specific metabolic functions. Proteins with a long polyglutamic tract
synthesized in the cells of patients with dentato-rubral and pallido-luysian atrophy, myotonic dystrophy
and Huntington disease interfere with transcription on the nuclear matrix. Down's syndrome is a
representative of the group of diseases with altered nuclear matrix protein spectrum.