| 1. |
- Karppinen, S. -M., et al.
(författare)
-
Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies
- 2006
-
Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 43:11, s. 856-862
-
Tidskriftsartikel (refereegranskat)abstract
- Background: BARD1 was originally identified as a BRCA1- interacting protein but has also been described in tumour-suppressive functions independent of BRCA1. Several studies have indicated that the BARD1 gene is a potential target for germline changes predisposing to breast and ovarian cancer. The C- terminal Cys557Ser change has previously been uncovered to associate with an increased risk of breast cancer and was recently shown to result in defective apoptotic activities. Aim and methods: Conformation- sensitive gel electrophoresis, minisequencing, TaqMan assays, denaturing high- performance liquid chromatography analysis and DNA sequencing were used to investigate the prevalence of the Cys557Ser allele in a large Nordic case - control study cohort consisting of 2906 patients with breast or ovarian cancer, 734 with prostate cancer, 188 with colorectal cancer, 128 men with breast cancer, and 3591 controls from Finland, Iceland, Denmark, Sweden and Norway. Results: The frequency of the BARD1 Cys557Ser variant seemed to increase among patients from families with breast or ovarian cancer lacking BRCA1 or BRCA2 mutations: a significant difference was obtained compared with controls ( 6.8% v 2.7%; p < 0.001; odds ratio ( OR) 2.6; 95% confidence interval (CI) 1.7 to 4.0) and with patients from BRCA1/ BRCA2 mutation- positive families ( 6.8% v 2.2%; p = 0.01; OR 3.2; 95% CI 1.2 to 8.3). In contrast, no major association with male breast, ovarian, colorectal or prostate cancer was observed. Additionally, a novel BARD1 allele resulting in Ser558Pro was identified in familial breast cancer cases. Conclusion: These results provide further evidence that BARD1 Cys557Ser confers a slightly increased risk of breast cancer in women.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Nahse, Viola, et al.
(författare)
-
ATPase activity of DFCP1 controls selective autophagy
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The endoplasmic reticulum protein DFCP1 is found on omegasomes implicated in autophagosome biogenesis, but its function has remained unknown. Here, Nahse et al. show that DFCP1 is an ATPase that mediates selective autophagy by promoting constriction of large omegasomes. Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Bock G., Roberts R.G., Kissling E., Achauer A., Alingahi J., Bruneton M., Friedrich W., Grad M. Guterch A., Hjelt S-E., Hyvönen T., Ikonen J-P., Komminaho K., Korja A, Heikkinen P., Kozolovaskaya E., Nevsky M.V., Pavlenkova N., Pedersen H., Plomerova J.
(författare)
-
Seismic probing of Archean and Proterozoic Lithosphere in Fennoscandia.
- 2001
-
Ingår i: EOS Transactions American Geophysical Union. - : American Geophysical Union. ; 82, s. 621,628-629
-
Tidskriftsartikel (refereegranskat)
|
|
| 10. |
- Bruneton, M., V. Farra, H. A. Pedersen & the SVEKALAPKO Seismic Tomography Working Group, (G. Bock, U. Achauer, A. Alinaghi, J. Ansorge, M. Bruneton, W. Friederich, M. Grad, A. Guterch, S.-E. Hjelt, T. Hyvönen, J.-P. Ikonen, E. Kissling, K. Komminaho, A.
(författare)
-
Non-linear surface wave phase velocity inversion based on ray theory.
- 2002
-
Ingår i: Geophys. J. Int. ; 151, s. 583-596
-
Tidskriftsartikel (refereegranskat)
|
|
