Related Experiment Video

Updated: Jun 28, 2026

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
09:45

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity

Published on: January 29, 2018

p38beta2-mediated phosphorylation and sumoylation of ATF7 are mutually exclusive

Barbara Camuzeaux1, Jessica Diring, Pierre-Jacques Hamard

  • 1Université de Strasbourg I, Institut Gilbert Laustriat, CNRS-UMR7175, Ecole Supérieure de Biotechnologie de Strasbourg, BP10413, Strasbourg Illkirch Cedex, France.

Journal of Molecular Biology
|October 28, 2008
PubMed

Insights

Activating transcription factor 7 (ATF7) activity is switched by antagonistic posttranslational modifications. Phosphorylation activates ATF7 by preventing sumoylation, enhancing TAF12 interaction and transcriptional activity.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Post-translational Modifications

Background:

  • Activating transcription factor 7 (ATF7) regulates gene expression by binding to specific DNA elements.
  • ATF7 activity is modulated by interactions with other proteins like TAF12 and by post-translational modifications such as sumoylation.
  • Sumoylation of ATF7 inhibits its transcriptional activity by restricting subcellular localization.

Purpose of the Study:

  • To elucidate the mechanism controlling the functional switch between ATF7 sumoylation and phosphorylation.
  • To identify kinases involved in ATF7 phosphorylation and characterize the phosphorylation process.
  • To understand how these modifications affect ATF7's interaction with TAF12 and its transcriptional output.

Main Methods:

  • Characterization of ATF7 multisite phosphorylation in its activation domain.
  • Identification of p38beta2 mitogen-activated protein kinase as a key player in ATF7 phosphorylation.
  • Analysis of ATF7 modification in response to epidermal growth factor (EGF) treatment.
  • Assessment of TAF12 association with modified ATF7 forms.

Main Results:

  • A two-step phosphorylation mechanism for the ATF7 activation domain was identified.
  • Epidermal growth factor (EGF) treatment triggers sequential phosphorylation of Thr53 and Thr51 residues.
  • Phosphorylation of Thr51 by p38beta2 mitogen-activated protein kinase prevents ATF7 sumoylation.
  • This phosphorylation event enhances the association of TAF12 with ATF7, leading to transcriptional activation.

Conclusions:

  • Sumoylation and phosphorylation represent antagonistic post-translational modifications governing ATF7 activity.
  • The phosphorylation cascade, initiated by an unknown kinase and completed by p38beta2 MAPK, serves as a switch to activate ATF7.
  • This mechanism highlights a novel regulatory pathway for transcription factors involving sequential phosphorylation and antagonism with sumoylation.

More Related Videos

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins08:12

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins

Published on: January 8, 2018

Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications09:29

Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications

Published on: May 18, 2017

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...