Please use this identifier to cite or link to this item: https://doi.org/10.1016/S1097-2765(03)00490-8
Title: Regulation of NF-κB Signaling by Pin1-Dependent Prolyl Isomerization and Ubiquitin-Mediated Proteolysis of p65/RelA
Authors: Ryo, A.
Suizu, F.
Perrem, K.
Liou, Y.-C. 
Wulf, G.
Lu, K.P.
Yoshida, Y.
Rottapel, R.
Yamaoka, S.
Issue Date: 2003
Source: Ryo, A., Suizu, F., Perrem, K., Liou, Y.-C., Wulf, G., Lu, K.P., Yoshida, Y., Rottapel, R., Yamaoka, S. (2003). Regulation of NF-κB Signaling by Pin1-Dependent Prolyl Isomerization and Ubiquitin-Mediated Proteolysis of p65/RelA. Molecular Cell 12 (6) : 1413-1426. ScholarBank@NUS Repository. https://doi.org/10.1016/S1097-2765(03)00490-8
Abstract: The transcription factor NF-κB is activated by the degradation of its inhibitor IκBα, resulting in its nuclear translocation. However, the mechanism by which nuclear NF-κB is subsequently regulated is not clear. Here we demonstrate that NF-κB function is regulated by Pin1-mediated prolyl isomerization and ubiquitin-mediated proteolysis of its p65/RelA subunit. Upon cytokine treatment, Pin1 binds to the pThr254-Pro motif in p65 and inhibits p65 binding to IκBα, resulting in increased nuclear accumulation and protein stability of p65 and enhanced NF-κB activity. Significantly, Pin1-deficient mice and cells are refractory to NF-κB activation by cytokine signals. Moreover, the stability of p65 is controlled by ubiquitin-mediated proteolysis, facilitated by a cytokine signal inhibitor, SOCS-1, acting as a ubiquitin ligase. These findings uncover two important mechanisms of regulating NF-κB signaling and offer new insight into the pathogenesis and treatment of some human diseases such as cancers.
Source Title: Molecular Cell
URI: http://scholarbank.nus.edu.sg/handle/10635/38232
ISSN: 10972765
DOI: 10.1016/S1097-2765(03)00490-8
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

423
checked on Dec 6, 2017

WEB OF SCIENCETM
Citations

416
checked on Nov 17, 2017

Page view(s)

82
checked on Dec 10, 2017

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.