KOSZTYU, Pavlína, Kateřina CETKOVSKÁ, Karen H. VOUSDEN and Stjepan ULDRIJAN. Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability. FEBS Letters. Netherlands: ELSEVIER SCIENCE BV, 2012, vol. 586, No 16, p. 2225-2231. ISSN 0014-5793. doi:10.1016/j.febslet.2012.05.034.
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Basic information
Original name Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability
Authors KOSZTYU, Pavlína (203 Czech Republic, guarantor, belonging to the institution), Kateřina CETKOVSKÁ (203 Czech Republic, belonging to the institution), Karen H. VOUSDEN (826 United Kingdom of Great Britain and Northern Ireland) and Stjepan ULDRIJAN (203 Czech Republic, belonging to the institution).
Edition FEBS Letters, Netherlands, ELSEVIER SCIENCE BV, 2012, 0014-5793.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 3.582
RIV identification code RIV/00216224:14110/12:00065570
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1016/j.febslet.2012.05.034
UT WoS 000306694800004
Keywords in English p53 degradation; Mdm2; Acidic domain; Mutagenesis; Ubiquitin ligase activity; Binding partner
Tags International impact
Changed by Changed by: Ing. Mgr. Věra Pospíšilíková, učo 9005. Changed: 10. 10. 2013 10:20.
Abstract
The exact role of the central acidic domain of Mdm2 in p53 degradation remains unclear. We therefore performed a systematic and comprehensive analysis of the acidic domain using a series of short deletions and found that only a minor part of the domain was indispensable for Mdm2-mediated p53 ubiquitylation. Moreover, we identified a short stretch of acidic amino acids required for p53 degradation but not ubiquitylation, indicating that, in addition to p53 ubiquitylation, the acidic domain might be involved in a critical post-ubiquitylation step in p53 degradation. Rather than representing a single functional domain, different parts of the acidic region perform separate functions in p53 degradation, suggesting that it might be possible to therapeutically target them independently.
Links
GA301/09/1324, research and development projectName: Funkce centrální domény onkoproteinu Mdm2 a jejích nových vazebných partnerů při regulaci nádorového supresoru p53
Investor: Czech Science Foundation
NS10236, research and development projectName: Terapeutický potenciál inhibice vybraných signálních drah v buňkách maligního melanomu
Investor: Ministry of Health of the CR
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