PubMed Journals: Cell

  Source:		PMID: 12757707

    		Cell. 2003 May 16;113(4):457-68.
			Interaction of Akt-phosphorylated ataxin-1
			with 14-3-3 mediates neurodegeneration in
			spinocerebellar ataxia type 1.

			Chen HK(1), Fernandez-Funez P, Acevedo SF,
			Lam YC, Kaytor MD, Fernandez MH, Aitken
			A, Skoulakis EM, Orr HT, Botas J, Zoghbi

			Author Information
			(1) Department of Molecular and Human Genetics,
			Baylor College of Medicine, Houston, TX
			77030, USA.

			Spinocerebellar ataxia type 1 (SCA1) is one of
			several neurological disorders caused by a
			CAG repeat expansion. In SCA1, this expansion
			produces an abnormally long polyglutamine
			tract in the protein ataxin-1. Mutant polyglutamine
			proteins accumulate in neurons, inducing
			neurodegeneration, but the mechanism underlying
			this accumulation has been unclear. We have
			discovered that the 14-3-3 protein, a
			multifunctional regulatory molecule, mediates
			the neurotoxicity of ataxin-1 by binding
			to and stabilizing ataxin-1, thereby slowing
			its normal degradation. The association
			of ataxin-1 with 14-3-3 is regulated by
			Akt phosphorylation, and in a Drosophila
			model of SCA1, both 14-3-3 and Akt modulate
			neurodegeneration. Our finding that
			phosphatidylinositol 3-kinase/Akt signaling
			and 14-3-3 cooperate to modulate the neurotoxicity
			of ataxin-1 provides insight into SCA1 pathogenesis
			and identifies potential targets for therapeutic

			PMID: 12757707 [Indexed for MEDLINE]

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