Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38
Klara Kirsch, Andras Zeke, Orsolya Toke, Peter Sok, Ashish Sethi, Anna Sebo, Ganesan Senthil Kumar, Peter Egri, Adam L Poti, Paul Gooley, Wolfgang Peti, Isabel Bento, Anita Alexa, Attila Remenyi
Nature Communications | NATURE RESEARCH | Published : 2020
Transcription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 transcription factors are phosphorylated by mitogen-activated protein kinases (MAPK) in their transactivation domains (TAD) at so-called phosphoswitches, which are a hallmark in response to growth factors, cytokines or stress. We show that the ATF2 TAD is controlled by functionally distinct signaling pathways (JNK and p38) through structurally different MAPK binding sites. Moreover, JNK mediated phosphorylation at an evolutionarily more recent site diminishes p38 binding and made the phosphoswitch ..View full abstract
Awarded by National Research Development and Innovation Office (NKFIH)
Awarded by Hungarian of Academy of Sciences
Awarded by National Institute of Health (NIH)
The authors thank Marie Bogoyevitch for her support and valuable discussions. This work was supported by the National Research Development and Innovation Office (NKFIH) grants (NN 114309, KKP 126963 awarded to A.R.), the Hungarian of Academy of Sciences (KEP-10/2019), and by a National Institute of Health (NIH) grant 1R01GM100910 to W.P.