Self-association of adenovirus 5 E1B-55 kDa as well as p53 is essential for their mutual interaction

Morawska-Onyszczuk, Magdalena

dc.contributor.advisor	Dobbelstein, Matthias Prof. Dr.	de
dc.contributor.author	Morawska-Onyszczuk, Magdalena	de
dc.date.accessioned	2009-12-15T06:53:42Z	de
dc.date.accessioned	2013-01-18T14:28:30Z	de
dc.date.available	2013-01-30T23:51:09Z	de
dc.date.issued	2009-12-15	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0006-B508-A	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3292
dc.format.mimetype	application/pdf	de
dc.language.iso	eng	de
dc.rights.uri	http://webdoc.sub.gwdg.de/diss/copyr_diss.html	de
dc.title	Self-association of adenovirus 5 E1B-55 kDa as well as p53 is essential for their mutual interaction	de
dc.type	doctoralThesis	de
dc.contributor.referee	Melchior, Frauke Prof. Dr.	de
dc.date.examination	2009-12-14	de
dc.subject.dnb	570 Biowissenschaften	de
dc.subject.dnb	Biologie	de
dc.description.abstracteng	P53 is at the center of the control systems that mediate the response to DNA damage, leading to cell cycle arrest or apoptosis. Virus infection can cause a DNA damage response through virus replication intermediates, but many viruses have evolved mechanisms to interfere with this response. The adenovirus type 5 E1B-55 kDa oncoprotein has several known functions during the viral life cycle, but it is mostly known for its ability to bind and inactivate the tumor suppressor p53. Together with another viral protein, E4orf6, E1B-55 kDa joins an E3 ubiquitin ligase complex and marks p53 for proteasomal degradation. In the absence of viral binding partners, E1B-55 kDa forms cytoplasmic clusters and sequesters p53 to them. Interestingly, E1B-55 kDa and p53 are each capable of forming oligomers. We mapped the oligomerization domain of E1B-55 kDa to the central portion of the protein. Disturbing E1B-55 kDa self-association by point mutations at residues 285/286 or 307 not only impairs its intracellular localization to the cytoplasmic clusters, but in addition its association with p53. Strikingly, tetramerization of p53 is also required for efficient association with E1B-55 kDa. Moreover, two different E1B-55 kDa mutants defective for p53 binding but proficient for oligomerization can trans-complement each other for p53 relocalization. We propose that the homo-oligomerization of each component enables the efficient interaction between E1B-55 kDa and p53 through increased avidity.	de
dc.contributor.coReferee	Wahl, Markus Prof. Dr.	de
dc.subject.topic	Molecular Biology & Neurosciences Program	de
dc.subject.eng	p53	de
dc.subject.eng	adenovirus	de
dc.subject.eng	oligomerization	de
dc.subject.eng	E1B-55 kDa	de
dc.subject.bk	42.13	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-2316-9	de
dc.identifier.purl	webdoc-2316	de
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	WF	de
dc.identifier.ppn	635404443	de

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Das Dokument erscheint in:

GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1115]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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