Dyrk1A Potentiates Steroid Hormone-Induced Transcription via the Chromatin Remodeling Factor Arip4
AUTOR(ES)
Sitz, Jan Hendrik
FONTE
American Society for Microbiology
RESUMO
Dyrk1A, a mammalian homolog of the Drosophila minibrain gene, encodes a dual-specificity kinase, involved in neuronal development and in adult brain physiology. In humans, a third copy of DYRK1A is present in Down syndrome (trisomy 21) and has been implicated in the etiology of mental retardation. To further understand this pathology, we searched for Dyrk1A-interacting proteins and identified Arip4 (androgen receptor-interacting protein 4), a SNF2-like steroid hormone receptor cofactor. Mouse hippocampal and cerebellar neurons coexpress Dyrk1A and Arip4. In HEK293 cells and hippocampal neurons, both proteins are colocalized in a speckle-like nuclear subcompartment. The functional interaction of Dyrk1A with Arip4 was analyzed in a series of transactivation assays. Either Dyrk1A or Arip4 alone displays an activating effect on androgen receptor- and glucocorticoid receptor-mediated transactivation, and Dyrk1A and Arip4 together act synergistically. These effects are independent of the kinase activity of Dyrk1A. Inhibition of endogenous Dyrk1A and Arip4 expression by RNA interference showed that both proteins are necessary for the efficient activation of androgen receptor- and glucocorticoid receptor-dependent transcription. As Dyrk1A is an activator of steroid hormone-regulated transcription, the overexpression of DYRK1A in persons with Down syndrome may cause rather broad changes in the homeostasis of steroid hormone-controlled cellular events.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=480880Documentos Relacionados
- Ribonucleic Acid Synthesis by Cucumber Chromatin: Developmental and Hormone-induced Changes 1
- Kinetics of Hormone-induced H+ Excretion 1
- Rapid Hormone-induced Hyperpolarization of the Oat Coleoptile Transmembrane Potential 1
- Runt-Related Transcription Factor 1 Regulates Luteinized Hormone-Induced Prostaglandin-Endoperoxide Synthase 2 Expression in Rat Periovulatory Granulosa Cells
- The adrenocorticotropic hormone-induced cortisol response in acute pancreatitis