Signalling and transport through the nuclear membrane

Csermely, Péter; Schnaider, Tamás; Szántó, Ildikó

doi:10.1016/0304-4157(95)00015-1

Cited by 53 publications

(30 citation statements)

References 446 publications

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“…It has been reported that calmodulin and its binding proteins are present in liver nuclei [Backs and Carafoli, 1987;Backs et al, 1990;Csermely et al, 1995]. If regucalcin can bind to calmodulin [Omura and Yamaguchi, 1998], regucalcin may have a role in the regulation of liver nuclear functions related to calmodulin.…”

Section: Discussionmentioning

confidence: 98%

Regulation of protein phosphatase activity by regucalcin localization in rat liver nuclei

Omura

Yamaguchi

1999

J. Cell. Biochem.

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The regulatory role of regucalcin on protein phosphatase activity in isolated rat liver nuclei was investigated. Phosphatase activity toward phosphotyrosine and phosphoserine was significantly increased by the addition of CaCl(2) (10(-5) and 10(-4) M) in the enzyme reaction mixture. Trifluoperazine (25 and 50 microM), an antagonist of calmodulin, significantly inhibited protein phosphatase activity toward phosphoserine, while it had no effect on the enzyme activity toward phosphotysine and phosphothreonine. Cyclosporin A (10(-6)-10(-4) M), an inhibitor of Ca(2+)/calmodulin-dependent protein phosphatase activity toward phosphoserine, but not phosphotyrosine and phosphoserine. Thus, Ca(2+)/calmodulin-dependent phosphatases were present in liver nuclei. Regucalcin (0.25 and 0.5 microM) had an inhibitory effect on liver nuclear phosphatase activity toward phosphotyrosine, phosphoserine, and phosphothreonine. The presence of anti-regucalcin monoclonal antibody (25 and 50 ng/ml) in the enzyme reaction mixture caused a significant elevation of nuclear phosphatase activity toward three phosphoaminoacids. An analysis with sodium sulfate-polyacrylamide gel electrophoresis suggested a possibility of localization of regucalcin in liver nuclei. Moreover, regucalcin was determined in liver nuclei using enzyme-linked immunoadsorbent assay. The present study demonstrates that the endogenous regucalcin inhibits phosphatase activity in the liver nuclei.

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Section: Discussionmentioning

confidence: 98%

Regulation of protein phosphatase activity by regucalcin localization in rat liver nuclei

Omura

Yamaguchi

1999

J. Cell. Biochem.

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“…It has been proposed that transformed cells have undergone alterations in their transport system, as a result of which a normally functioning inhibitor has been switched off. Due to these changes, nuclear transport of proteins may be promoted or hindered in cancer cells (45). It can be hypothesized that in normal cells apoptin is associated to and͞or modified by one or more cellular factor(s), resulting in its localization within perinuclear structures.…”

Section: Resultsmentioning

confidence: 99%

Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells

Oorschot

Fischer

Grimbergen

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

199

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The chicken anemia virus protein apoptin induces a p53-independent, Bcl-2-insensitive type of apoptosis in various human tumor cells. Here, we show that, in vitro, apoptin fails to induce programmed cell death in normal lymphoid, dermal, epidermal, endothelial, and smooth-muscle cells. However, when normal cells are transformed they become susceptible to apoptosis by apoptin. Long-term expression of apoptin in normal human fibroblasts revealed that apoptin has no toxic or transforming activity in these cells. In normal cells, apoptin was found predominantly in the cytoplasm, whereas in transformed and malignant cells it was located in the nucleus, suggesting that the localization of apoptin is related to its activity. These properties make apoptin a potential agent for the treatment of a large number of tumors, also those lacking p53 and͞or overexpressing Bcl-2.Apoptosis (or programmed cell death) is an active and programmed physiological process for eliminating superfluous, altered, or malignant cells (1). Apoptosis is characterized by shrinkage of cells, segmentation of the nucleus, condensation, and cleavage of DNA into domain-sized fragments in most cells followed by internucleosomal degradation. Finally, the apoptotic cells fragment into membrane-enclosed bodies, which are rapidly phagocytosed by neighboring cells (2-4).The apoptotic process can be initiated by a variety of regulatory stimuli (5, 6). Changes in cell-survival rate play an important role in human pathogenesis, e.g. in cancer development, which is caused by enhanced cell proliferation but also by decreased cell death (7-10). A variety of chemotherapeutic agents and radiation have been demonstrated to induce apoptosis in tumor cells, in many instances via the action of wild-type p53 (11-15). Most tumors, however, acquire a mutation in p53 during their development, often correlated with poor response to cancer therapy (16)(17)(18). In several leukemias a high expression level of the proto-oncogene Bcl-2 is associated with a strong resistance to various apoptosis-inducing chemotherapeutic agents (19)(20)(21)(22). Apoptin, a 14-kDa basic and proline-rich protein (23) derived from the chicken anemia virus, can induce apoptosis in chicken and human malignant cell lines (24,25). We have established that apoptosis induced by apoptin is p53-independent (26) and cannot be blocked by 28). Therefore, apoptin is a potential antitumor agent. To explore this possibility further, we have examined the in vitro apoptotic activity of apoptin in normal human cells versus transformed human cells. MATERIALS AND METHODSCell Culture. Human primary T cells were isolated from six normal blood donors by Ficol centrifugation and grown in RPMI medium 1640 containing 6% human serum and 0.8 g͞ml phytohemagglutinin. After 3 days, the medium was changed, and 300 units͞ml of interleukin-2 were added (29). Human umbilical-cord vascular endothelial cells (HUVEC) and smooth-muscle cells (HSMC) were isolated from umbilical cords as described (30). HUVEC were grown in M199 ...

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“…A number of studies have provided evidence suggesting roles for the activation of nuclear PKC in nuclear functions involving phosphorylation of transcription factors and DNA replication factors (46). Also it has been shown that the activation of nuclear PKC is correlated with an increase in nuclear DG.…”

Section: Characterization Of Pld Activity In Rat Liver and Rat Ascitesmentioning

confidence: 99%

Nuclear ADP-ribosylation Factor (ARF)- and Oleate-dependent Phospholipase D (PLD) in Rat Liver Cells

Banno

Tamiya‐Koizumi

Oshima

et al. 1997

Journal of Biological Chemistry

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Two forms of phospholipase D (PLD) have been found to be present in nuclei isolated from rat hepatocytes by measuring phosphatidylbutanol produced from exogenous radiolabeled phosphatidylcholine in the presence of butanol. In nuclear lysates from either rat liver or ascites hepatoma AH 7974 cells, the PLD activity was markedly stimulated by a recombinant ADP-ribosylation factor (rARF) in the presence of the guanosine 5-O-(3-thiotriphosphate) (GTP␥S) and phosphatidylinositol 4,5-bisphosphate. ATP and phorbol-12-myristate 13-acetate had no synergistic effect on this PLD activity. On the other hand, the nuclear PLD was stimulated by unsaturated fatty acids, especially by oleic acid. The ARF-dependent nuclear PLD activity was increased in the S-phase of the regenerating rat liver after partial hepatectomy and also was much higher in AH 7974 cells than in the resting rat liver. In contrast, the levels of the oleate-dependent PLD activity remained constant throughout the cell cycle in liver regeneration. The intranuclear levels of the stimulating proteins of the nuclear PLD activity, e.g. ARF, RhoA, and protein kinase C␦ increased in the S-phase of the regenerating liver. These results suggested that the nuclear ARFdependent PLD activity may be associated with cell proliferation.It has been known that cell nuclei contain a variety of enzymes generating lipid second messengers, such as sphingomyelinase (1), phospholipase A2 (2), PI 1 -specific phospholipase C (3-6) and lipid kinases (7). Growth factors seem to be able to affect the phosphoinositide metabolism in nuclei, suggesting a subtle regulation during cell activation (8, 9). In addition, accumulation of diacylglycerol (DG) in nuclei and translocation of protein kinase C to them have been demonstrated in a variety of cell types (10, 11). A large rise in mass of DG, with only small changes in mass of phosphoinositides, suggested a source of DG other than polyphosphoinositides, for example, phosphatidylcholine (PC), in nuclei (12). A recent study (13) has demonstrated that phosphatidylethanol formation from phosphatidylcholine, which was specifically catalyzed by phospholipase D (PLD) in the presence of ethanol, was induced by PMA in nuclei isolated from kidney cells and that nuclei possess the ability to generate DG and phosphatidic acid through the PLD:phosphatidic acid phosphohydrolase pathway. Thus, upon cell stimulation with agonists, the enzymes involving PC metabolism are considered to be activated in the nucleus as well as in the plasma membrane.It was demonstrated that PLD activity can be regulated by several factors (14, 15); oleate, small G proteins (ARF and Rho family), phosphatidylinositol 4,5-bisphosphate (PIP 2 ), phosphatidylethanolamine (PE), Ca 2ϩ , protein kinase C, protein tyrosine kinase. Recently, two different types of PLD, oleatedependent and ARF-dependent, were isolated from rat brain membranes (16). The oleate-dependent PLD was purified from pig lung microsomes (17), and ARF-dependent PLD activity was found to be abundant in Golgi-enriched ...

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Signalling and transport through the nuclear membrane

Cited by 53 publications

References 446 publications

Regulation of protein phosphatase activity by regucalcin localization in rat liver nuclei

Regulation of protein phosphatase activity by regucalcin localization in rat liver nuclei

Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells

Nuclear ADP-ribosylation Factor (ARF)- and Oleate-dependent Phospholipase D (PLD) in Rat Liver Cells

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