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|Title:||Regulation of NF-κB Signaling by Pin1-Dependent Prolyl Isomerization and Ubiquitin-Mediated Proteolysis of p65/RelA||Authors:||Ryo, A.
|Issue Date:||2003||Citation:||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|
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