Редактирование: DYRK3

Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC 2.7.12.1) (Regulatory erythroid kinase) (REDK)

==Publications==

{{medline-entry
|title=[[DYRK1A]] and [[DYRK3]] promote cell survival through phosphorylation and activation of [[SIRT1]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20167603
|abstract=[[DYRK1A]] (the dual specificity tyrosine phosphorylation-regulated kinase 1A) plays an important role in body growth and brain physiology. Overexpression of this kinase has been associated with the development of Down syndrome in both human and animal models, whereas single copy loss-of-function of [[DYRK1A]] leads to increased apoptosis and decreased brain size. Although more than a dozen of [[DYRK1A]] targets have been identified, the molecular basis of its involvement in neuronal development remains unclear. Here we show that [[DYRK1A]] and another pro-survival member of the DYRK family, [[DYRK3]], promote cell survival through phosphorylation and activation of [[SIRT1]], an NAD( )-dependent protein deacetylase that is essential in a variety of physiological processes including stress response and energy metabolism. [[DYRK1A]] and [[DYRK3]] directly phosphorylate [[SIRT1]] at Thr(522), promoting deacetylation of p53. A [[SIRT1]] phosphorylation mimetic ([[SIRT1]] T522D) displays elevated deacetylase activity, thus inhibiting cell apoptosis. Conversely, a [[SIRT1]] dephosphorylation mimetic ([[SIRT1]] T522V) fails to mediate DYRK-induced deacetylation of p53 and cell survival. We show that knockdown of endogenous [[DYRK1A]] and [[DYRK3]] leads to hypophosphorylation of [[SIRT1]], sensitizing cells to DNA damage-induced cell death. We also provide evidence that phosphorylation of Thr(522) activates [[SIRT1]] by promoting product release, thereby increasing its enzymatic turnover. Taken together, our findings provide a novel mechanism by which two anti-apoptotic DYRK members promote cell survival through direct modification of [[SIRT1]]. These findings may have important implications in understanding the molecular mechanisms of tumorigenesis, Down syndrome, and aging.
|mesh-terms=* Acetylation
* Aging
* Amino Acid Substitution
* Animals
* Apoptosis
* Brain
* Cell Line
* Cell Survival
* DNA Damage
* Disease Models, Animal
* Down Syndrome
* Enzyme Activation
* Humans
* Mice
* Mutation, Missense
* Organ Size
* Phosphorylation
* Protein-Serine-Threonine Kinases
* Protein-Tyrosine Kinases
* Sirtuin 1
* Tumor Suppressor Protein p53

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857074
}}