상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

The mechanism of p53 rescue by SUSP4

Authors 

Do-Hyoung KimChewook LeeSi-Hyung LeeK T KimJ J HanEun Ji ChaJi Eun LimYe-Jin ChoS H HongKyou Hoon Han

Publisher 

Wiley-Blackwell

Issue Date 

2017

Citation 

Angewandte Chemie International Edition

Keywords 

intrinsically disordered proteinNMR spectroscopyp53pre-structured motifSUSP4

Abstract 

p53 is an important tumor-suppressor protein deactivation of which by mdm2 results in cancers. A SUMO-specific protease 4 (SUSP4) was shown to rescue p53 from mdm2-mediated deactivation, but the mechanism is unknown. The discovery by NMR spectroscopy of a “p53 rescue motif” in SUSP4 that disrupts p53-mdm2 binding is presented. This 29-residue motif is pre-populated with two transient helices connected by a hydrophobic linker. The helix at the C-terminus binds to the well-known p53-binding pocket in mdm2 whereas the N-terminal helix serves as an affinity enhancer. The hydrophobic linker binds to a previously unidentified hydrophobic crevice in mdm2. Overall, SUSP4 appears to use two synergizing modules, the p53 rescue motif described here and a globular-structured SUMO-binding catalytic domain, to stabilize p53. A p53 rescue motif peptide exhibits an anti-tumor activity in cancer cell lines expressing wild-type p53. A pre-structures motif in the intrinsically disordered proteins is thus important for target recognition

ISSN 

1433-7851

Link 

http://dx.doi.org/10.1002/anie.201607819

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)