Sumoylation delays the ATF7 transcription factor subcellular localization and inhibits its transcriptional activity.
Over the past few years, small ubiquitin-like modifier (SUMO) modification has emerged as an important regulator of diverse pathways and activities including protein localization and transcriptional regulation. We identified a consensus sumoylation motif (IKEE), located within the N-terminal activation domain of the ATF7 transcription factor and thus investigated the role of this modification. ATF7 is a ubiquitously expressed transcription factor, homologous to ATF2, that binds to CRE elements within specific promoters. This protein is able to heterodimerize with Jun or Fos proteins and its transcriptional activity is mediated by interaction with TAF12, a subunit of the general transcription factor TFIID. In the present article, we demonstrate that ATF7 is sumoylated in vitro (using RanBP2 as a E3-specific ligase) and in vivo. Moreover, we show that ATF7 sumoylation affects its intranuclear localization by delaying its entry into the nucleus. Furthermore, SUMO conjugation inhibits ATF7 transactivation activity by (i) impairing its association with TAF12 and (ii) blocking its binding-to-specific sequences within target promoters.
Hamard
Pierre-Jacques
PJ
Institut Gilbert Laustriat, Ecole Supérieure de Biotechnologie de Strasbourg, UMR7175 CNRS-ULP, BP10413, 67412 Strasbourg Illkirch Cedex, France.
Boyer-Guittaut
Michaël
M
Camuzeaux
Barbara
B
Dujardin
Denis
D
Hauss
Charlotte
C
Oelgeschläger
Thomas
T
Vigneron
Marc
M
Kedinger
Claude
C
Chatton
Bruno
B
D051696:Activating Transcription Factors / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
C427752:ATF7 protein, human; D051696:Activating Transcription Factors; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D025842:SUMO-1 Protein; C094493:ran-binding protein 2; D044767:Ubiquitin-Protein Ligases