THE SERINE THREONINE PHOSPHATASE INHIBITOR CALYCULIN-A INDUCES RAPID DEGRADATION OF I-KAPPA-B-BETA - REQUIREMENT OF BOTH THE N-TERMINAL ANDC-TERMINAL SEQUENCES/

Authors
Citation
Ew. Harhaj et Sc. Sun, THE SERINE THREONINE PHOSPHATASE INHIBITOR CALYCULIN-A INDUCES RAPID DEGRADATION OF I-KAPPA-B-BETA - REQUIREMENT OF BOTH THE N-TERMINAL ANDC-TERMINAL SEQUENCES/, The Journal of biological chemistry, 272(9), 1997, pp. 5409-5412
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
272
Issue
9
Year of publication
1997
Pages
5409 - 5412
Database
ISI
SICI code
0021-9258(1997)272:9<5409:TSTPIC>2.0.ZU;2-8
Abstract
Signal-initiated activation of the transcription factor NF-kappa B is mediated through proteolysis of its cytoplasmic inhibitory proteins I kappa B alpha and I kappa B beta. While most NF-kappa B inducers trigg er the degradation of I kappa B alpha, only certain stimuli are able t o induce the degradation of I kappa B beta. The degradation of I kappa B alpha is targeted by its site-specific phosphorylations, although t he mechanism underlying the degradation of I kappa B beta remains elus ive. In the present study, we have analyzed the effect of phosphatase inhibitors on the proteolysis of I kappa B beta. We show that the seri ne/threonine phosphatase inhibitor calyculin A induces the hyperphosph orylation and subsequent degradation of I kappa B beta in both human J urkat T cells and the murine 70Z-3 preB cells, which is associated wit h the nuclear expression of active NF-kappa B. The calyculin A-mediate d degradation of I kappa B beta is further enhanced by the cytokine tu mor necrosis factor-alpha (TNF-alpha), although TNF-alpha alone is una ble to induce the degradation of I kappa B beta. Mutational analyses h ave revealed that the inducible degradation of I kappa B beta induced by calyculin A, and TNF-alpha requires two N-terminal serines (serines 19 and 23) that are homologous to the inducible phosphorylation sites present in I kappa B alpha. Furthermore, the C-terminal 51 amino acid residues, which are rich in serines and aspartic acids, are also requ ired for the inducible degradation of I kappa B beta. These results su ggest that the degradation signal of I kappa B beta may be controlled by the opposing actions of protein kinases and phosphatases and that b oth the N- and C-terminal sequences of I kappa B beta are required for the inducible degradation of this NF-kappa B inhibitor.