Binding of Translationally Controlled Tumour Protein to the N-Terminal Domain of HDM2 Is Inhibited by Nutlin-3

被引：12

作者：

Funston, Garth ^{[1
]}

Goh, Walter ^{[2
]}

Wei, Siau Jia ^{[2
]}

Tng, Quah Soo ^{[2
]}

Brown, Christopher ^{[2
]}

Tong, Loh Jiah ^{[3
]}

Verma, Chandra ^{[3
,4
,5
]}

Lane, David ^{[2
]}

Ghadessy, Farid ^{[2
]}

机构：

[1] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Cambridge CB2 2QQ, England

[2] ASTAR, p53Lab, Singapore, Singapore

[3] ASTAR, Bioinformat Inst, Singapore, Singapore

[4] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore

[5] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore

来源：

PLOS ONE | 2012年 / 7卷 / 08期

关键词：

HISTAMINE-RELEASING FACTOR; CANCER CELLS; ANTIAPOPTOTIC ACTIVITY; DNA-DAMAGE; IN-VIVO; TCTP; P53; MDM2; GROWTH; UBIQUITINATION;

D O I：

10.1371/journal.pone.0042642

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Translationally Controlled Tumour Protein (TCTP), a highly conserved protein present in all eukaryotic organisms, has a number of intracellular and extracellular functions including an anti-apoptotic role. TCTP was recently shown to interact with both p53 and HDM2, inhibiting auto-ubiquitination of the latter and thereby promoting p53 degradation. In this study, we further investigated the interaction between TCTP and HDM2, mapping the reciprocal binding sites of TCTP and HDM2. TCTP primarily interacts with the N-terminal, p53-binding region of HDM2 through its highly basic domain 2. Furthermore, we discovered that Nutlin-3, a small molecule known to promote apoptosis and cell cycle arrest by blocking binding between HDM2 and p53, has a similar inhibitory effect on the interaction of HDM2 and TCTP. This result may provide an additional explanation of how Nutlin-derived compounds currently in clinical trials function to promote apoptosis in cancer cells.

引用

页数：8

共 34 条

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