Proteomics

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Intricate coupling between the transactivation and basic-leucine zipper domains governs the CK2-dependent phosphorylation of ATF4

ABSTRACT: Most transcription factors possess at least one long intrinsically disordered transactivation domain that binds to a variety of co-activators and co-repressors and plays a key role in modulating the transcriptional activity. Despite the crucial importance of these mechanisms, the structural and functional basis of transactivation domain in yet poorly understood. Here, we focused on ATF4/CREB-2, an essential transcription factor for cellular stress adaptation. We found that the N-terminal region of the transactivation domain is involved in transient long-range interactions with the basic-leucine zipper domain. In vitro phosphorylation assays with the protein kinase CK2 show that the presence of the basic-leucine zipper domain is required for optimal phosphorylation of the transactivation domain. This study uncovers the intricate coupling existing between the transactivation and basic-leucine zipper domains of ATF4 and highlights its potential functional relevance.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Steven Siang  

LAB HEAD: Julien Roche

PROVIDER: PXD029704 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

Intricate coupling between the transactivation and basic-leucine zipper domains governs phosphorylation of transcription factor ATF4 by casein kinase 2.

Siang Steven S   Underbakke Eric S ES   Roche Julien J  

The Journal of biological chemistry 20220122 3

Most transcription factors possess at least one long intrinsically disordered transactivation domain that binds to a variety of coactivators and corepressors and plays a key role in modulating the transcriptional activity. Despite the crucial importance of these domains, the structural and functional basis of transactivation remains poorly understood. Here, we focused on activating transcription factor 4 (ATF4)/cAMP response element-binding protein-2, an essential transcription factor for cellul  ...[more]

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