Не работает мышка что делать. Почему не работает мышка на ноутбуке. Не работает беспроводная мышка. Почему не работает клавиатура. Почему не работает клавиатура на компьютере. Не работают некоторые кнопки клавиатуры. Как обшить ванну панелями. Скажите чем обшить стены в ванной. Обшить ванну пластиком фото. Приложения для android бесплатно. Скачать лучшие приложения для android. Приложение для планшетов android. Горнолыжные курорты финляндии. Лучшие горнолыжные курорты финляндии цены. Лучшие курорты финляндии. Как лечить воспаление легких. Воспаление легких симптомы основные. Воспаление легких лечение. Уроки по python. Учим python с нуля быстро. Как изучать быстро язык Python. Проблемы с сердцем симптомы. Основные признаки проблем с сердцем. Проблемы с клапаном сердца.

The Cul4A–DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity

M Malatesta, A Peschiaroli, EM Memmi, J Zhang, A Antonov, DR Green, NA Barlev, AV Garabadgiu, P Zhou, G Melino and F Bernassola


Oncogene (2012), 1–6


Читать статью


The Cullin4A (cul4A)-dependent ligase (CDL4A) E3 has been implicated in a variety of biological processes, including cell cycle progression and DNA damage response. Remarkably, CDL4A exerts its function through both proteolytic and non-proteolytic events. Here, we show that the p53 family member p73 is able to interact with the CDL4A complex through its direct binding to the receptor subunit DNA-binding protein 1 (DDB1). As a result, the CDL4A complex is able to monoubiquitylate p73. Modification of
p73 by CDL4A-mediated ubiquitylation does not affect p73 protein stability, but negatively regulates p73-dependent transcriptional activity. Indeed, genetic or RNA interference-mediated depletion of DDB1 induces the expression of several p73 target genes in a
p53-independent manner. In addition, by exploiting a bioinformatic approach, we found that elevated expression of Cul4A in human breast carcinomas is associated with repression of p73 target genes. In conclusion, our findings add a novel insight into the
regulation of p73 by the CDL4A complex, through the inhibition of its transcriptional function.


1 Chen X, Zhang Y, Douglas L, Zhou P. UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. J Biol Chem 2001; 276: 48175–48182.

2 Leung-Pineda V, Huh J, Piwnica-Worms H. DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress. Cancer Res 2009; 69: 2630–2637.

3 Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R et al. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 2003; 113: 357–367.

4 Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature 2006; 443: 590–593.

5 Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H. CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat Cell Biol 2006; 8: 1277–1283.

6 Lee J, Zhou P. DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol Cell 2007; 26: 775–780.

7 Li T, Chen X, Garbutt KC, Zhou P, Zheng N. Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 2006; 124: 105–117.

8 Hu J, McCall CM, Ohta T, Xiong Y. Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol 2004; 6: 1003–1009.

9 Cang Y, Zhang J, Nicholas SA, Kim AL, Zhou P, Goff SP. DDB1 is essential for genomic stability in developing epidermis. Proc Natl Acad Sci USA 2007; 104: 2733–2737.

10 Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T. CDK Inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. J Biol Chem 2008; 283: 29045–29052.

11 Liu L, Lee S, Zhang J, Peters SB, Hannah J, Zhang Y et al. CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis. Mol Cell 2009; 34: 451–460.

12 Choi SH, Wright JB, Gerber SA, Cole MD. Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells. Genes Dev 2010; 24: 1236–1241.

13 Hannah J, Zhou P. Regulation of DNA damage response pathways by the cullin-RING ubiquitin ligases. DNA Repair (Amst) 2009; 8: 536–543.

14 Cang Y, Zhang J, Nicholas SA, Bastien J, Li B, Zhou P et al. Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells. Cell 2006; 127: 929–940.

15 Kopanja D, Stoyanova T, Okur MN, Huang E, Bagchi S, Raychaudhuri P. Proliferation defects and genome instability in cells lacking Cul4A. Oncogene 2009; 28: 2456–2465.

16 Jost CA, Marin MC, Kaelin Jr WG. p73 is a simian [correction of human] p53-related protein that can induce apoptosis. Nature 1997; 389: 191–194.

17 Melino G, Bernassola F, Ranalli M, Yee K, Zong WX, Corazzari M et al. p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation. J Biol Chem 2004; 279: 8076–8083.

18 Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D et al. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 2005; 7: 363–373.

19 Tomasini R, Tsuchihara K, Wilhelm M, Fujitani M, Rufini A, Cheung CC et al. TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev 2008; 22: 2677–2691.

20 Rossi M, De Laurenzi V, Munarriz E, Green DR, Liu YC, Vousden KH et al. The ubiquitin-protein ligase Itch regulates p73 stability. EMBO J 2005; 24: 836–848.

21 Peschiaroli A, Scialpi F, Bernassola F, Pagano M, Melino G. The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73. Oncogene 2009; 28: 3157–3166.

22 Nag A, Bagchi S, Raychaudhuri P. Cul4A physically associates with MDM2 and participates in the proteolysis of p53. Cancer Res 2004; 64: 8152–8155.

23 van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F et al. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol 2006; 8: 1064–1073.

24 Salghetti SE, Caudy AA, Chenoweth JG, Tansey WP. Regulation of transcriptional activation domain function by ubiquitin. Science 2001; 293: 1651–1653.

25 Greer SF, Zika E, Conti B, Zhu XS, Ting JP. Enhancement of CIITA transcriptional function by ubiquitin. Nat Immunol 2003; 4: 1074–1082.

26 Hershkovitz Rokah O, Shpilberg O, Granot G. NAD(P)H quinone oxidoreductase protects TAp63gamma from proteasomal degradation and regulates TAp63-gamma-dependent growth arrest. PLoS One 2010; 5: e11401.

27 Chen LC, Manjeshwar S, Lu Y, Moore D, Ljung BM, Kuo L et al. The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers. Cancer Res 1998; 58: 3677–3683.

28 Banks D, Wu M, Higa LA, Gavrilova N, Quan J, Ye T et al. L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes. Cell Cycle 2006; 5: 1719–1729.

29 Busuttil V, Droin N, McCormick L, Bernassola F, Candi E, Melino G et al. NF-kappaB inhibits T-cell activation-induced, p73-dependent cell death by induction of MDM2. Proc Natl Acad Sci USA 2010; 107: 18061–18066.

30 Sayan AE, Paradisi A, Vojtesek B, Knight RA, Melino G, Candi E. New antibodies recognizing p73: comparison with commercial antibodies. Biochem Biophys Res Commun 2005; 330: 186–193.

Прочитано 4317 раз
Оцените материал
(0 голосов)
Опубликовано в СТАТЬИ
Авторизуйтесь, чтобы получить возможность оставлять комментарии


Управление научных исследований СПбГТИ (ТУ)

Горячие новости

Приборное оснащение лаборатории

Rambler's Top100
//'+ 'Рейтинг@Mail.ru<\/a><\/p>');})(window,navigator,document);//]]>