ATF4 Degradation Relies on a Phosphorylation-dependent Interaction with the SCF(betaTrCP) Ubiquitin Ligase

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2001 Mar 10

PMID 11238952

Citations 112

Authors

I Lassot

E Segeral

C Berlioz-Torrent

H Durand

L Groussin

T Hai

R Benarous

F Margottin-Goguet

Affiliations

Soon will be listed here.

Abstract

The ubiquitin-proteasome pathway regulates gene expression through protein degradation. Here we show that the F-box protein betaTrCP, the receptor component of the SCF E3 ubiquitin ligase responsible for IkappaBalpha and beta-catenin degradation, is colocalized in the nucleus with ATF4, a member of the ATF-CREB bZIP family of transcription factors, and controls its stability. Association between the two proteins depends on ATF4 phosphorylation and on ATF4 serine residue 219 present in the context of DSGXXXS, which is similar but not identical to the motif found in other substrates of betaTrCP. ATF4 ubiquitination in HeLa cells is enhanced in the presence of betaTrCP. The F-box-deleted betaTrCP protein behaves as a negative transdominant mutant that inhibits ATF4 ubiquitination and degradation and, subsequently, enhances its activity in cyclic AMP-mediated transcription. ATF4 represents a novel substrate for the SCF(betaTrCP) complex, which is the first mammalian E3 ubiquitin ligase identified so far for the control of the degradation of a bZIP transcription factor.

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