The nuclear matrix and apoptosis

Abstract

Apoptosis is a form of active cell death, genetically encoded, that plays a key role during several physiological and pathological conditions. During the apoptotic process, striking morphological and biochemical changes take place in the cell nucleus. However, the molecular mechanisms underlying these changes have escaped clarification for many years. Recently, attention has been devoted to identifying the modifications that occur during apoptosis in the nuclear matrix, a mainly proteinaceous framework structure which is thought to play a fundamental role in organizing nuclear structure and function. In this review, we focus our attention on the biochemical and morphological changes detected in the nuclear matrix during the apoptotic process. Particular emphasis will be placed on the proteolysis that some nuclear matrix proteins undergo early during the apoptotic process, as well as on the detachment of DNA loops from the matrix by the action of endonuclease(s). Future research in this field may provide important information about the principal mechanisms that cause nuclear destruction in apoptotic cells.

Scaffold/Matrix Attachment Regions (S/MARs): Relevance for Disease and Therapy

“…The existence of a nuclear skeleton was first proposed about 60 years ago (Zbarsky and Debov 1948), and methods for the preparation of such an entity have been developed and refined ever since (reviewed by Martelli et al 1996). We will maintain the idea that a nuclear skeleton acts as a dynamic support for many specialized reactions as the most suggestive model to guide the reader through this review.…”

Nuclear Diacylglycerol Kinase-θ Is Activated in Response to α-Thrombin

“…For example, DGK has been shown to be modulated in response to various growth factors and hormones, such as noradrenaline (5,9,10), interleukin-2 (6,(11)(12)(13), concanavalin A (14), insulinlike growth factor-I (15), and leptin (16). Additional support for the notion that DGKs are involved in signaling derives from the observations that DGKs have been found in signaling complexes associated with Rac, phosphatidylinositol 5-kinase, Rho-GDI (17), and Ras-GRP (18), and that they are involved in the regulation of cellular growth (6,11,12,15,19). Clearly, understanding the mechanisms that regulate DGK in various signaling cascades will be essential to delineating the physiological roles of this enzyme.…”

S/MAR-binding properties of Sox2 and its involvement in apoptosis of human NT2 neural precursors

“…10,[28][29][30] It has also been suggested that degradation and/or modification of MAR-binding proteins may play a key role in the molecular mechanisms of nuclear disassembly during apoptosis. [1][2][3][4]6,15 Recently, using a well-characterized model of apoptosis, anti-Fas treatment of Jurkat cells, we examined the sequence integrity of several genes (the c-myc proto-oncogene, high-mobility group phosphoprotein, protamine gene cluster, pyruvate dehydrogenase alpha subunit and low-molecular-weight acid phosphatase), which all contain sequences highly similar to the 25 bp BUR element of the IgH gene and known binding site of SATB1 protein. 6 In all cases the DNA breaks appear in close proximity to these sites, concomitant with proteolysis of SATB1 and consistent with MARs being the initiation sites of the DNA cleavage process.…”

“…[11][12][13][14][15] Most of them are components of the nuclear matrix and several have been shown to undergo site-specific proteolysis in the early stage of apoptosis. 3,4,16,17 Consequently, this process has been temporally linked to the initiation of DNA cleavage, suggesting that the latter may be a consequence of the loss of the proteinacious insulation.…”