Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ

Abstract : A protein in RAW macrophages, which became phosphorylated in response to LPS, was identified as the RNA-binding protein termed Deleted in AZoospermia (DAZ) Associated Protein 1 (DAZAP1). The phosphorylation of this protein was prevented by specific inhibition of MKK1, indicating that it was phosphorylated via the classical MAP kinase cascade. Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 at two Thr-Pro sequences (Thr269 and Thr315) and that both sites became phosphorylated in HEK293 cells in response to PMA or EGF, or RAW macrophages in response to LPS. Phosphorylation induced by each stimulus was prevented by two structurally distinct inhibitors of MKK1 (PD 184352 and U0126), demonstrating that DAZAP1 is a physiological substrate for ERK1/ERK2. The mutation of Thr269 and Thr315 to Asp or the phosphorylation of these residues caused DAZAP1 to dissociate from its binding partner DAZ. DAZ interacts with Poly(A) binding protein (PABP) and thereby stimulate the translation of mRNAs containing short Poly(A) tails (Collier et al, 2005, EMBO J. 24, 2656-2666). Here we showed that DAZ cannot bind simultaneously to DAZAP1 and PABP and suggest that the phosphorylation-induced dissociation of DAZ and DAZAP1 may allow the former to stimulate translation by interacting with PABP.
Mots-clés : Life Sciences
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Article dans une revue
Biochemical Journal, Portland Press, 2006, 399 (2), pp.265-273. 〈10.1042/BJ20060681〉
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Simon Morton, Huei-Ting Yang, Ntsane Moleleki, David G Campbell, Philip Cohen, et al.. Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ. Biochemical Journal, Portland Press, 2006, 399 (2), pp.265-273. 〈10.1042/BJ20060681〉. 〈hal-00478590〉

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