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Wyświetlanie 1-5 z 5
Tytuł:
The essential function of Swc4p - a protein shared by two chromatin-modifying complexes of the yeast Saccharomyces cerevisiae - resides within its N-terminal part
Autorzy:
Miciałkiewicz, Arkadiusz
Chełstowska, Anna
Powiązania:
https://bibliotekanauki.pl/articles/1040724.pdf
Data publikacji:
2008
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
chromatin remodeling complexes
histone acetylation
mutagenesis
mutant phenotype
Opis:
The Swc4p protein, encoded by an essential gene, is shared by two chromatin-remodeling complexes in Saccharomyces cerevisiae cells: NuA4 (nucleosome acetyltransferase of H4) and SWR1. The SWR1 complex catalyzes ATP-dependent exchange of the nucleosomal histone H2A for H2AZ (Htz1p). The activity of NuA4 is responsible mainly for the acetylation of the H4 histone but also for the acetylation of H2A and H2AZ. In this work we investigated the role of the Swc4p protein. Using random mutagenesis we isolated a collection of swc4 mutants and showed that the essential function of Swc4p resides in its N-terminal part, within the first 269 amino acids of the 476-amino acid-long protein. We also demonstrated that Swc4p is able to accommodate numerous mutations without losing its functionality under standard growth conditions. However, when swc4 mutants were exposed to methyl methanesulfonate (MMS), hydroxyurea or benomyl, severe growth deficiencies appeared, pointing to an involvement of Swc4p in many chromatin-based processes. The mutants' phenotypes did not result from an impairment of histone acetylation, as in the mutant which bears the shortest isolated variant of truncated Swc4p, the level of overall H4 acetylation was unchanged.
Źródło:
Acta Biochimica Polonica; 2008, 55, 3; 603-612
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Two Gln187 mutants of human soluble APRIL inhibit proliferation of lung carcinoma A549 cells
Autorzy:
Dai, Shuangshuang
Zheng, Yingru
Chen, Bin
Gao, Min
Zhang, Yan
Zhang, Li
Gong, Wei
He, Fengtain
Powiązania:
https://bibliotekanauki.pl/articles/1040492.pdf
Data publikacji:
2009
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
APRIL
Gln187 mutant of sAPRIL
anti-tumor activity
Opis:
Soluble APRIL (sAPRIL), the active form of a proliferation-inducing ligand (APRIL), is implicated in the proliferation of tumor cells. Suppressing APRIL function has been considered as a potential strategy for the therapy of APRIL-associated tumors. In the present study, we generated human sAPRIL and its two mutants, Gln187-D-sAPRIL (Gln187 deleted) and Gly187-sAPRIL (Gln187 replaced by Gly). In vitro experiments showed that the two mutants had similar specific binding capacity to lung carcinoma A549 cells compared to the wild-type sAPRIL, and both, especially Gly187-sAPRIL, exhibited significant antagonistic effect on sAPRIL-induced tumor cell proliferation in a dose-dependent manner, which might be predominantly mediated by blocking sAPRIL-induced MEK and ERK phosphorylation but not p38MAPK or JNK signaling. In vivo experiments with nude mice bearing A549 cell-derived xenograft tumor showed that only the Gly187-sAPRIL mutant could significantly suppress the tumor growth. These results suggest that Gln187 may be a crucial amino acid in APRIL-mediated tumor cell proliferation via the MEK-ERK signaling pathway and that the sAPRIL mutants may serve as novel potential antagonists of APRIL for the therapy of APRIL-associated cancers.
Źródło:
Acta Biochimica Polonica; 2009, 56, 4; 703-710
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Defective Brca2 influences topoisomerase I activity in mammalian cells*.
Autorzy:
Rahden-Staroń, Iwonna
Szumiło, Maria
Grosicka, Emilia
Kraakman - van der Zwet, Maria
Zdzienicka, Małgorzata
Powiązania:
https://bibliotekanauki.pl/articles/1043656.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
camptothecin
V-C8 mutant
topoisomerase I
Brca2 gene
Opis:
The Chinese hamster cell mutant V-C8 is defective in the Brca2 gene (Kraakman-van der Zwet et al., 2002, Cell Biol.; 22: 669). Here we report that V-C8 cells were 10-fold more sensitive to camptothecin, an inhibitor of topoisomerase I, than the parental V79 cells. The level of the relaxation activity of topoisomerase I in nuclear extracts was also lower (4-fold) in V-C8 than V79 cells, in spite of the fact that the level of the topoisomerase I protein was the same in these cells. The survival of V-C8 cells in the presence of camptothecin, the sensitivity of V-C8 topoisomerase I to camptothecin, and the level of the relaxation activity in V-C8 nuclear extract were almost completely restored by transfection of V-C8 cells with the murine Brca2 gene or by the transfer of human chromosome 13 providing the BRCA2 gene. These results indicate that the observed changes in the topoisomerase I activity in V-C8 are due to the defective function of the Brca2 gene.
Źródło:
Acta Biochimica Polonica; 2003, 50, 1; 139-144
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Modulation of the voltage-dependent anion-selective channel by cytoplasmic proteins from wild type and the channel depleted cells of Saccharomyces cerevisiae.
Autorzy:
Kmita, Hanna
Budzińska, Małgorzata
Stobienia, Olgierd
Powiązania:
https://bibliotekanauki.pl/articles/1043619.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
VDAC-depleted mutant
reconstituted system
Saccharomyces cerevisiae
voltage dependent anion selective channel (VDAC)
mitochondria
yeast
Opis:
It is well known that effective exchange of metabolites between mitochondria and the cytoplasm is essential for cell physiology. The key step of the exchange is transport across the mitochondrial outer membrane, which is supported by the voltage-dependent anion-selective channel (VDAC). Therefore, it is clear that the permeability of VDAC must be regulated to adjust its activity to the actual cell needs. VDAC-modulating activities, often referred to as the VDAC modulator, were identified in the intermembrane space of different organism mitochondria but the responsible protein(s) has not been identified as yet. Because the VDAC modulator was reported to act on VDAC of intact mitochondria when added to the cytoplasmic side it has been speculated that a similar modulating activity might be present in the cytoplasm. To check the speculation we used mitochondria of the yeast Saccharomyces cerevisiae as they constitute a perfect model to study VDAC modulation. The mitochondria contain only a single isoform of VDAC and it is possible to obtain viable mutants devoid of the channel (Δpor1). Moreover, we have recently characterised a VDAC-modulating activity located in the intermembrane space of wild type and Δpor1 S. cerevisiae mitochondria. Here, we report that the cytoplasm of wild type and Δpor1 cells of S. cerevisiae contains a VDAC-modulating activity as measured in a reconstituted system and with intact mitochondria. Since quantitative differences were observed between the modulating fractions isolated from wild type and Δpor1 cells when they were studied with intact wild type mitochondria as well as by protein electrophoresis it might be concluded that VDAC may influence the properties of the involved cytoplasmic proteins. Moreover, the VDAC-modulating activity in the cytoplasm differs distinctly from that reported for the mitochondrial intermembrane space. Nevertheless, both these activities may contribute efficiently to VDAC regulation. Thus, the identification of the proteins is very important.
Źródło:
Acta Biochimica Polonica; 2003, 50, 2; 415-424
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
p53-dependent suppression of the human calcyclin gene (S100A6): the role of Sp1 and of NFκB
Autorzy:
Króliczak, Weronika
Pietrzak, Maciej
Puzianowska-Kuznicka, Monika
Powiązania:
https://bibliotekanauki.pl/articles/1040715.pdf
Data publikacji:
2008
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
gene suppression
wild type and mutant p53
Sp1
calcyclin gene (S100A6)
NFκB
Opis:
Calcyclin (S100A6) is believed to participate in cell cycle control. It was, however, unclear if its expression depends on p53, a key regulator of apoptosis and cell cycle. We therefore performed transcription regulation assays in HeLa cells and found that wild type p53 suppressed the S100A6 promoter up to 12-fold in a dose-dependent manner. In contrast, the well-characterized V143A, R175H, R249S, and L344A p53 mutants cloned from human cancers suppressed this promoter with a 6 to 9-fold lower efficiency. All the sites mediating the p53-dependent suppression were contained in the -167 to +134 fragment of the S100A6 promoter. Separate overexpression of either Sp1 or of NFκB only partially counteracted the p53 inhibitory effect on the S100A6 promoter, while simultaneous overexpression of both these transactivators resulted in a complete abolishment of the p53 inhibitory effect on this promoter. Sp1 and NFκB binding to the probes resembling their putative binding sites present in the S100A6 promoter was decreased in the presence of wild type p53. We propose that the suppression of S100A6 is yet another mechanism by which p53 inhibits proliferation. Insufficient suppression of this gene by p53 mutants could well be responsible for calcyclin overexpression and cell cycle deregulation observed in cancer tissues.
Źródło:
Acta Biochimica Polonica; 2008, 55, 3; 559-570
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
    Wyświetlanie 1-5 z 5

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