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Molecular and Cellular Biology, July 2004, p. 5821-5834, Vol. 24, No. 13
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.13.5821-5834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Dyrk1A Potentiates Steroid Hormone-Induced Transcription via the Chromatin Remodeling Factor Arip4

Jan Hendrik Sitz,1 Marcel Tigges,1 Karsten Baumgärtel,{dagger} Leonid G. Khaspekov,1,2 and Beat Lutz1*

Molecular Genetics of Behavior, Max Planck Institute of Psychiatry, 80804 Munich, Germany,1 Brain Research Institute, Russian Academy of Medical Sciences, 105064 Moscow, Russia2

Received 16 February 2004/ Accepted 26 March 2004

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.

* Corresponding author. Mailing address: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany. Phone: 49 89 30 622-640. Fax: 49 89 30 622-610. E-mail: lutz{at}mpipsykl.mpg.de.

{dagger} Present address: Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.

Molecular and Cellular Biology, July 2004, p. 5821-5834, Vol. 24, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.13.5821-5834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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