Minibrain/DYRK1A-Gen: Kandidatengen für die mentale Retardierung bei Down-Syndrom?

Zusammenfassung:

DYRK1A ist das erste Mitglied einer jüngst beschriebenen Familie von Proteinkinasen mit dualer Spezifität. Das humane Gen für DYRK1A ist in einer für das Down-Syndrom kritischen Region des Chromosoms 21 (21q22.2) lokalisiert. durch seine Verwandtschaft zu dem Drosophila-Gen minibrain (Mnb), dessen Mutation zu spezifischen Defekten der Neurogenese führt, und aufgrund funktioneller Untersuchungen transgener Mäuse wird DYRK1A als Kandidatengen für die mentale Retardierung des Down-Syndroms diskutiert. Charakteristisch für die Kinase ist ihre Fähigkeit der Autophosphorylierung an Tyrosinresten und der Substratphosphorylierung an Serin-/Threoninresten. Ihre exakte zelluläre Funktion ist bisher nicht bekannt. Man weiß jedoch, dass DYRK1A in den Zellkern transportiert wird und nimmt an, dass sie Einfluss auf den Zellzyklus und damit auf das Wachstum und die Differenzierung von Geweben besitzt. Ihre pathogenetische Bedeutung für das Down-Syndrom bedarf weiterer Klärung.

DYRK1A is the first member of a novel subfamily of protein kinases with dual specificity. The human gene for DYRK1A is located in the “Down syndrome critical region” (21q22.2). Due to its relationship to the Drosophila gene minibrain (Mnb), whose mutation results in specific defects in neurogenesis, and based on functional experiments on transgenic mice, DYRK1A is discussed as a candidate gene for mental retardation in Down syndrome. The kinase is characterized by its ability to catalyze tyrosine-directed autophosphorylation as well as phosphorylation of serine/threonine residues in substrates. Its exact cellular function is yet unknown. DYRK1A is, however, known to be translocated into the nucleus and supposed to be involved in the control of cell growth and development. The pathogenetic impact of DYRK1A on Down syndrome needs further elucidation.

Down-Syndrom - Trisomie 21 - DYRK1A - Minibrain

Down Syndrome - Trisomy 21 - DYRK1A - Minibrain

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