uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
A transactivation-deficient mouse model provides insights into trp53 regulation and function
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. (Tumorigenesis)
Show others and affiliations
2000 (English)In: Nature Genetics, ISSN 1061-4036, Vol. 26, no 1, 37-43 p.Article in journal (Refereed) Published
Abstract [en]

The gene Trp53 is among the most frequently mutated and studied genes in human cancer, but the mechanisms by which it suppresses tumour formation remain unclear. We generated mice with an allele encoding changes at Leu25 and Trp26, known to be essential for transcriptional transactivation and Mdm2 binding, to enable analyses of Trp53 structure and function in vivo. The mutant Trp53 was abundant, its level was not affected by DNA damage and it bound DNA constitutively; however, it showed defects in cell-cycle regulation and apoptosis. Both mutant and Trp53-null mouse embryonic fibroblasts (MEFs) were readily transformed by oncogenes, and the corresponding mice were prone to tumours. We conclude that the determining pathway for Trp53 tumour-suppressor function in mice requires the transactivation domain.

Place, publisher, year, edition, pages
2000. Vol. 26, no 1, 37-43 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-51447DOI: 10.1038/79152PubMedID: 10973245OAI: oai:DiVA.org:uu-51447DiVA: diva2:79356
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-01-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Genetics and Pathology
In the same journal
Nature Genetics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 170 hits
ReferencesLink to record
Permanent link

Direct link