Wyniki wyszukiwania - Biblioteka Nauki

1

High mobility group proteins stimulate DNA cleavage by apoptotic endonuclease DFF40-CAD due to HMG-box interactions with DNA

100%

Kalinowska-Herok M. , Widlak P.

Acta Biochimica Polonica

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2008

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tom 55

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nr 1

EN

The DFF40/CAD endonuclease is primarily responsible for internucleosomal DNA cleavage during the terminal stages of apoptosis. It has been previously demonstrated that the major HMG-box-containing chromatin proteins HMGB1 and HMGB2 stimulate naked DNA cleavage by DFF40/CAD. Here we investigate the mechanism of this stimulation and show that HMGB1 neither binds to DFF40/CAD nor enhances its ability for stable binding to DNA. Comparison of the stimulatory activities of different truncated forms of HMGB1 protein indicates that a structural array of two HMG-boxes is required for such stimulation. HMG-boxes are known to confer specific local distortions of DNA structure upon binding. Interestingly, the presence of DNA strand cross-links formed by cisplatin or transplatin, which may somehow mimic distortions induced by HMG-boxes, also affects DNA cleavage by the nuclease. The data presented suggest that changes induced in DNA conformation upon HMG-box binding makes the substrate more accessible to cleavage by DFF40/CAD nuclease and thus may contribute to preferential linker DNA cleavage during apoptosis.

2

Prewencja genetyczna raka piersi

80%

Pamuła-Piłat J. , Kalinowska-Herok M. , Mazur M. , Tęcza K.

Laboratorium Medyczne

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2018

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tom nr 3

50--56

PL

Rak piersi jest jednym z najczęściej wykrywanych nowotworów u kobiet. Część zachorowań na nowotwór złośliwy sutka uwarunkowana jest czynnikami genetycznymi. Identyfikacja osób z silną genetyczną predyspozycją do zachorowania umożliwia wczesne wykrycie nowotworu, wdrożenie profilaktyki przeciwnowotworowej czy modyfikację sposobu leczenia.

EN

Breast cancer is one of the most commonly diagnosed cancers in women. Part of breast cancer cases are caused by genetic factors. The identification of patients with strong genetic predisposition to the disease enables the early detection of cancer, implementation of anticancer prophylaxis or modification of treatment.

3

High mobility group proteins stimulate DNA cleavage by apoptotic endonuclease DFF40/ CAD due to HMG-box interactions with DNA

80%

Kalinowska-Herok M. , Hanus J. , Szoltysek K.-A. , Widlak P.

Acta Biochimica Polonica

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2007

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tom 54

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nr Supplement 4

4

Using yeast two-hybrid system to identify novel proteins putatively interacting with the apoptotic nuclease DFF40/CAD

71%

Hanus J. , Slusarczyk A. , Kalinowska-Herok M. , Chelstowska A. , Widlak P.

Acta Biochimica Polonica

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2007

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tom 54

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nr Supplement 4

5

TNFalpha-induced activation of NFkappaB protects against UV-induced apoptosis specifically in p53-proficient cells

61%

Szoltysek K. , Pietranek K. , Kalinowska-Herok M. , Pietrowska M. , Kimmel M. , Widlak P.

Acta Biochimica Polonica

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2008

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tom 55

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nr 4

741-748

EN

The signaling pathways that depend on p53 or NFκB transcription factors are essential components of cellular responses to stress. In general, p53 is involved in either activation of cell cycle arrest or induction of apoptosis, while NFκB exerts mostly anti-apoptotic functions; both regulatory pathways apparently interfere with each other. Here we aimed to analyze the effects of NFκB activation on DNA damage-induced apoptosis, either p53-dependent or p53-independent, in a set of human cell lines. Four cell lines, HCT116 and RKO colon carcinoma, NCI-H1299 lung carcinoma and HL60 myeloblastoma, each of them in two congenic variants either containing or lacking transcriptionally competent p53, were used. Cells were incubated with TNFα cytokine to activate NFκB and then treated with ultraviolet or ionizing radiation to induce apoptosis, which was assessed by measurement of the sub-G1 cell fraction. We observed that treatment with TNFα resulted in a significant reduction in the frequency of apoptotic cells in UV-irradiated p53-proficient lines (with exception of the UV-resistant NCI-H1299 cells). This anti-apoptotic effect was lost when cells were pretreated with parthenolide, an inhibitor of NFκB activation. In marked contrast, TNFα-pretreatment of p53-deficient lines resulted in an increased frequency of apoptotic cells after UV irradiation (with exception of HL60 cells). Such anti- and pro-apoptotic influence of TNFα was less obvious in cells treated with ionizing radiation. The data clearly indicates functional interference of both signaling pathways upon the damage-induced apoptotic response, yet the observed effects are both cell type- and stimulus-specific.