VRK1 phosphorylates Tip60 acetyltransferase and promotes its accumulation in response to both DNA damage and mitogens

Autor: García González, Raúl, Campillo-Marcos, Ignacio, Lazo, Pedro A.
Rok vydání: 2017
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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Popis: Resumen del póster presentado al 1st Joint Meeting of the French-Portuguese-Spanish Biochemical and Molecular Biology Societies y al XL Spanish Society of Biochemistry and Molecular Biology (SEBBM) Congress, celebrado en Barcelona (España) del 23 al 26 de octubre de 2017.
Eukaryotic DNA is highly organized in a packaged nucleoprotein structure known as chromatin. This chromatin is subjected to dynamics that regulate its degree of compaction in processes such as cell proliferation or DNA damage repair. Chromatin dynamics are mainly governed by an epigenetic set of heritable chemical modifi cations that occurs in the tail of the histones. One of the most important epigenetic modifications is acetylation which, generally, allows chromatin decompacting of those regions that either need to be expressed during cell cycle or repaired. This modification is carried out by a family of enzymes called histone acetyl-transferases (HATs). However, the mechanism by which the activity of HATs is regulated in response to mitogens or DNA damage is unknown. In this context, a kinase could be responsible for activating these histone-modifiers, since it is well-known that phosphorylation is an important modification that regulates protein activity in many cellular processes. Among all the kinases present in cells, we hypothesize that the kinase VRK1 is a candidate to perform such a role, based on current data that supports that this Ser-Thr kinase has an important role in both DNA damage response and cell proliferation. To probe this hypothesis, we have studied the eff ect of VRK1 on Tip60, one of the most important HATs. Our results show that VRK1 interacts and phosphorylates Tip60 in response to both DNA damage and mitogens. Further, VRK1 knock-down induces Tip60 degradation, suggesting that this phosphorylation is important for Tip60 stability. Altogether these data indicates that VRK1 may be a key component in the regulation of Tip60 activity, which could play an important role in chromatin dynamics during both cell proliferation and DNA damage response.
Databáze: OpenAIRE
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