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Nuclear receptors: integration of multiple signalling pathways through phosphorylation.

Abstract：

:Nuclear receptors (NRs) orchestrate the transcription of specific gene networks in response to binding of their cognate ligand. They also act as mediators in a variety of signalling pathways through integrating diverse phosphorylation events. NR phosphorylation concerns all three major domains, the N-terminal activation function (AF-1), the ligand-binding and the DNA binding domains. Often, phosphorylation of NRs by kinases that are associated with general transcription factors (e.g. cdk7 within TFIIH), or activated in response to a variety of signals (MAPKs, Akt, PKA, PKC), facilitates the recruitment of coactivators or of components of the transcription machinery and, therefore, cooperates with the ligand to enhance transcription activation. But phosphorylation can also contribute to the termination of the ligand response through inducing DNA dissociation or NR degradation or through decreasing ligand affinity. These different modes of regulation reveal an unexpected complexity of the dynamics of NR-mediated transcription. In addition, deregulation of NR phosphorylation may impact their action in certain diseases or cancers.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Rochette-Egly C

doi

10.1016/s0898-6568(02)00115-8

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

355-66

issue

4

eissn

0898-6568

issn

1873-3913

pii

S0898656802001158

journal_volume

15

pub_type

杂志文章,评审

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