Dynamic continuity of nuclear and mitotic matrix proteins in the cell cycle

Abstract

The eukaryotic cell nucleus is a membrane-enclosed compartment containing the genome and associated molecules supported by a highly insoluble filamentous network known as the nucleoskeleton or nuclear matrix. The nuclear matrix is believed to play roles in maintaining nuclear architecture and organizing nuclear metabolism. Recently, advances in microscopic techniques and the availability of new molecular probes have made it possible to localize functional domains within the nuclear matrix and demonstrate dynamic interactions between both soluble and insoluble components involved in the control of multiple nuclear transactions. Like the cytoplasm and its skeleton, the nucleoplasm is highly structured and very crowded with an equally complex skeletal framework. In fact, there is growing evidence that the two skeletal systems are functionally contiguous, providing a dynamic cellular matrix connecting the cell surface with the genome. If we impose cell cycle dynamics upon this skeletal organization, it is obvious that the genome and associated nuclear matrix must undergo a major structural transition during mitosis, being disassembled and/or reorganized in late G2 and reassembled again in daughter nuclei. However, recent evidence from our laboratory and elsewhere suggests that much of the nuclear matrix is used to form the mitotic apparatus (MA). Indeed, both facultative and constitutive matrix-associated proteins such as NuMA, CENP-B, CENP-F, and the retinoblastoma protein (Rb) associate within and around the MA. During mitosis, the nuclear matrix proteins may either become inert "passengers" or assume critical functions in partitioning the genome into newly formed G1 nuclei. Therefore, we support the view that the nuclear matrix exists as a dynamic architectural continuum, embracing the genome and maintaining cellular regulation throughout the cell cycle.

Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity

“…CENP-F is a faculative kinetochore protein that gradually accumulates during the G2 and M phases, localizing in the kinetochore region of the centromeres and in the spindle midzone (2,22). CENP-F is able to interact with CENP-E and the spindle check-point component Bub1 (23).…”

Characterization of Skeletor: a novel nuclear protein implicated in mitotic spindle assembly

“…Recent studies suggest that there is a "dynamic continuity" between the nuclear matrix and the proteins of the mitotic apparatus (Mancini et al, 1996). During interphase, the microtubules are organized into networks throughout the cytoplasm, with their minus ends near the centrosome, and their plus ends towards the periphery of the cell.…”

“…One such case is SIR4, a yeast protein containing serine-rich region that is in a multiprotein chromatin binding complex regulating mating-type genes (Marshall et al, 1987). Acidic regions as well, such as the one found in the human centromere autoantigen CENP-B, have been implicated in direct interactions with chromosomal scaffold or chromatin bound proteins (Mancini et al, 1996).…”

Genoma funcional e análise "in silico" na caracterização e no isolamento de genes envolvidos em gliomas humanos

“…Utilizando a tecnologia de hibridização subtrativa (SSH), um doutorando do laboratório (Cleber Vedoy, Processo Fapesp N°96/04713-4) obteve genes regulados por glicocorticóides que atuam no controle da diferenciação celular (Vedoy & Sogayar, 2002 (Berezney & Coffey, 1974). Contendo 98% de proteína, 0,1% de DNA, 0,5% de fosfolipídeos e 1,2% de RNA, a matriz nuclear é um suporte tridimensional que possui funções fundamentais em muitas atividades celulares, como: determinação da morfologia nuclear, estabilização e orientação do DNA durante a replicação, organização de complexos regulatórios de genes e síntese de RNA (Mancini et al, 1996;Replogle-Schwab et al, 1996). A matriz nuclear coordena, também, diferentes processos que ocorrem na cromatina, a qual se encontra sob rígido controle do ciclo celular (Loidl & Eberharter, 1995).…”

“…A matriz nuclear coordena, também, diferentes processos que ocorrem na cromatina, a qual se encontra sob rígido controle do ciclo celular (Loidl & Eberharter, 1995). Assim, por exemplo, o produto do gene retinoblastoma (pRB) está associado com a matriz nuclear durante o ciclo celular (Mancini et al, 1996). Algumas proteínas que interagem com pRB também estão associadas com a matriz nuclear, incluindo oncoproteínas virais inativadas (antígeno large T de SV-40, proteína E1a de adenovírus e proteína E7 de papiloma humano), laminina A1C (Ozaki et al, 1994) e p84 (Durfee et al, 1994).…”