Wyniki wyszukiwania - Biblioteka Nauki

1

Relationships between immunologically distinct P53 forms and P21 WAF1 and PCNA expression in ovarian carcinomas

100%

Harlozinska A. , Bar J. , Montenarh M. , Kartarius S.

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nr Suppl.

2

Potential suppressor gene loci and human prostate neoplasms

75%

Brys M. , Krajewska W. M.

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1997

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tom 02

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nr 4

EN

The biology of prostate cancer is still poorly understood. Allelic loss studies indicate that there likely exist multiple sites harbouring candidate tumour suppressor genes (TSG), some of which may have an important role in primary tumours, and some in late stages of prostate cancer. The recent studies on the localization of potential TSG in neoplastic transformation of prostate comprise chromosome regions 7q, 8p, l0p/q, 16q, 17q, and 18q. In connection with accumulation of genetic changes affecting functioning of critical TSG, the multistep cancer progression hypothesis is a useful starting point in efforts to understand the biology of the neoplastic lesions of prostate.

3

Prospects for p53-based cancer therapy

75%

Stoklosa T. , Golab J.

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nr 2

EN

The p53 tumor suppressor plays the role of a cellular hub which gathers stress signals such as damage to DNA or hypoxia and translates them into a complex response. p53 exerts its action mainly as a potent transcription factor. The two major outcomes of p53 activity are highlighted: cell cycle arrest and apoptosis. During malignant transformation p53 or p53-pathway related molecules are disabled extremely often. Mutations in p53 gene are present in every second human tumor. A mutant form of p53 may not only negate the wild type p53 function but may play additional role in tumor progression. Therefore p53 represents a relatively unique and specific target for anticancer drug design. Current approaches include several different molecules able to restore p53 wild-type conformation and activity. Such small molecule drugs hold great promise in treating human tumors with dysfunction of p53 pathway in the near future.

4

Advantage of a baculovirus expression system for protein-protein interaction studies. Involvement of posttranslational phosphorylation in the interaction between wt p53 protein and poly[ADP-ribose] polymerase-1

75%

Schmid G. , Wojciechowski J. , Wesierska-Gadek J.

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nr 3

EN

We recently observed an interaction between poly(ADP-ribose) polymerase-1 (PARP-1) and the tumor suppressor p53 protein. However, more extensive studies on both proteins, especially those on characterization of their domains involved in the interaction were difficult due to very low expression levels of p53 in mammalian cells. Therefore, we generated recombinant proteins for such studies. To clarify which domains of human PARP-1 and of human wild-type (wt) p53 were involved in this protein-protein interaction, we generated baculoviral constructs encoding full length or distinct functional domains of both proteins. Full length PARP-1 was simultaneously coexpressed in insect cells with full length wt p53 protein or its distinct truncated fragments and vice versa. Reciprocal immunoprecipitation of Sf9 cell lysates revealed that the central and carboxy-terminal fragments of p53 each were sufficient to confer binding to PARP-1, whereas the amino-terminal part harbouring the transactivation functional domain was dispensable. On the other hand, the amino-terminal and central fragments of PARP-1 were both necessary for complex formation with p53 protein. Since the most important features of p53 protein are regulated by phosphorylation, we addressed the question whether its phosphorylation is essential for the binding between the two proteins. Baculovirally expressed wt p53 was post-translationally modified. At least six distinct p53 isomers were resolved by immunoblotting following two-dimensional separation of baculovirally expressed wt p53 protein. Using specific phospho-serine antibodies, we identified phosphorylation of baculovirally expressed p53 protein at five distinct sites. To define the role of p53 phosphorylation, pull-down assays using untreated and dephosphorylated p53 protein were performed. Dephosphorylated p53 failed to bind PARP-1, indicating that complex formation between the two proteins was regulated by phosphorylation of p53. The marked phosphorylation of p53 at Ser392 observed in unstressed cells suggests that the phosphorylated carboxy-terminal part of p53 undergoes complex formation with PARP-1 resulting in masking of the NES and thereby preventing its export.

5

Molecular basis of gynaecological malignancies: endometrial cancer

75%

Pirog E. C.

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tom 44

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nr 1-2

6

Gene 53p and its role in tumor disease

63%

Wojciechowski M. , Walkuska G.

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nr 3

7

Prognostic significance of DAPK and RASSF1A promoter hypermethylation in non-small cell lung cancer [NSCLC]

63%

Niklinska W. , Naumnik W. , Sulewska A. , Kozlowski M. , Pankiewicz W. , Milewski R.

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nr 2

275-280

8

PML shuttles between nuclear bodies and the cytoplasm

63%

Stuurman N. , Floore A. , Middelkoop E. , Van Driel R. , De Jong L.

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nr 2

EN

Nuclear bodies are electron dense, spherical structures with a diameter between 0.2 and 1.0 µm. The function of these nuclear domains is unclear. One class of nuclear bodies contains the tumor suppressor protein PML. Besides in the nucleus, a small number of PML-containing structures of about the same size as nuclear bodies is also present in the cytoplasm. We have investigated whether PML is transported from the nucleus to the cytoplasm and/or vice versa. To this end we injected the PML-specific mAb 5E10 into the cytoplasm of living cells. Subsequently, we monitored translocation of the antibody across the nuclear envelope by indirect immunofluorescent microscopy. It is well known that antibodies in the cytoplasm of living cells do not enter the nucleus, unless as a complex with a karyophilic protein. We observed accumulation into PML-containing nuclear bodies of 5E10 microinjected into the cytoplasm. Control rabbit IgG and a mAb specific for lamin B2 were not translocated to the nucleus. All nuclear PML bodies were labeled simultaneously by 5E10 with gradually increased intensity in time. Labeling of PML-containing nuclear bodies by 5E10 microinjected into the cytoplasm was not affected by inhibition of protein synthesis. These results suggest that the 5E10 antigen PML shuttles between the nucleus and cytoplasm, indicating that nuclear bodies are dynamic structures.

9

Contribution of molecular biology to cancer diagnosis and treatment

63%

Radzikowski C.

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nr 4

10

Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer

51%

Laudanski P. , Kowalczuk O. , Klasa-Mazurkiewicz D. , Miczek T. , Rysak-Luberowicz D. , Garbowicz M. , Baranowski W. , Charkiewicz R. , Szamatowicz J. , Chyczewski L.

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nr 2