Dyrk1A Positively Stimulates ASK1-JNK Signaling Pathway during Apoptotic Cell Death

다국어 초록 (Multilingual Abstract)

Dual-specificity tyrosine (Y)-phosphorylation-regulated protein kinase 1A (Dyrk1A) is the mammalian homologue of Drosophila melanogaster minibrain and its human gene is mapped to the Down syndrome critical region of chromosome 21. Dyrk1A phosphorylates several transcription factors, including NFAT and CREB and a number of cytosolic proteins such as APP, tau, and Ձ-synuclein. Although Dyrk1A is involved in the control of cell growth and postembryonic neurogenesis, its potential role during cell death and signaling pathway is not clearly understood. In the present study, we show that Dyrk1A is activated under the condition of apoptotic cell death. In addition, Dyrk1A is coupled to JNK1 activation, and directly interacts with apoptosis signal- regulating kinase 1 (ASK1). Moreover, Dyrk1A positively regulates ASK1-mediated JNK1-signaling, and appears to directly phosphorylate ASK1. These data indicate that Dyrk1A regulates cell death through facilitating ASK1-mediated signaling events.

참고문헌 (Reference)

1 Woods YL, "The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site" 355 : 597-607, 2001

2 Hashimoto Y, "The cytoplasmic domain of Alzheimer's amyloid-β protein precursor causes sustained apoptosis signal-regulating kinase 1/c-Jun NH2-terminal kinase-mediated neurotoxic signal via dimerization" 306 : 889-902, 2003

3 Holtzman DA, "Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae" 122 : 635-644, 1993

4 Zhang L, "Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins" 8511-8515, 1999

5 Ip YT, "Signal transduction by the c-Jun N-terminal kinase (JNK) -- from inflammation to development" 10 : 205-219, 1998

6 Song JJ, "Role of glutaredoxin in metabolic oxidative stress. Glutaredoxin as a Sensor of Oxidative Stress Mediated by H2O2" 277 : 46566-46575, 2002

7 Kanamoto T, "Role of apoptosis signalregulating kinase in regulation of the c-Jun N-terminal kinase pathway and apoptosis in sympathetic neurons" 20 : 196-204, 2000

8 정광철, "Regulation of the proapoptotic activity of Huntingtin interacting protein 1 by Dyrk1 and caspase-3 in hippocampal neuroprogenitor cells" 81 : 62-72, 200507

9 Noguchi T, "Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death" 280 : 37033-37040, 2005

10 안영수, "Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells" AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 276 (276): 39819-39824, 200110

11 Kim EK, "Positive regulation of ASK1-mediated c-Jun NH2-terminal kinase signaling pathway by the WDrepeat protein Gemin5" 14 : 1518-1528, 2007

12 Murakami N, "Phosphorylation of amphiphysin I by minibrain kinase/dual-specificity tyrosine phosphorylationregulated kinase, a kinase implicated in Down syndrome" 281 : 23712-23724, 2006

13 Altafaj X, "Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome." 10 : 1915-1923, 2001

14 Arron JR, "NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21" 441 : 595-600, 2006

15 Roat E, "Mitochondrial alterations and tendency to apoptosis in peripheral blood cells from children with Down syndrome" 581 : 521-525, 2007

16 Tejedor F, "Minibrain: a new protein kinase family involved in postembryonic neurogenesis in Drosophila" 14 : 287-301, 1995

17 Saitoh M, "Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1" 17 : 2596-2606, 1998

18 Takeda K, "Involvement of ASK1 in Ca2＋-induced p38 MAP kinase activation" 582 : 161-166, 2004

19 Ichijo H, "Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways" 275 : 90-94, 1997

20 Schuchmann S, "Increased mitochondrial superoxide generation in neurons from trisomy 16 mice:a model of down's syndrome.Free Radical Biology and Medicine" 28 : 235-250, 2000

21 Zhang R, "Hsp90-Akt phosphorylates ASK1 and inhibits ASK1-mediated apoptosis" 24 : 3954-3963, 2005

22 Lorenzi HA, "Hippocampal hypocellularity in the Ts65Dn mouse originates early in development.Brain Research" 1104 : 153-159, 2006

23 Smith DJ, "Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome" 16 : 28-36, 1997

24 Raths S, "End3 and End4: Two mutants defective in receptor-mediated and fluid- phase endocytosis in Saccharomyces cerevisiae" 120 : 55-65, 1993

25 정광철, "Dyrk1A phosphorylates α-synuclein and enhances intracellular inclusion formation" AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 281 (281): 33250-33257, 200611

26 Park J, "Dyrk1A overexpression in immortalized hippocampal cells produces the neuropathological features of Down syndrome" 36 : 270-279, 2007

27 Fotaki V, "Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice" 22 : 6636-6647, 2002

28 Chen-Hwang MC, "Dynamin is a minibrain kinase/dual specificity yak1-related kinase 1A substrate" 277 : 17597-17604, 2002

29 Ryoo SR, "Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer disease" 104 : 1333-1344, 2008

30 Ryoo SR, "DYRK1A-mediated hyperphosphorylation of Tau: A Functional Link Between Down Syndrome and Alzheimer Disease" 282 : 34850-34857, 2007

31 Kelly PA, "DYRK1A enhances the mitogen-activated protein kinase cascade in PC12 cells by forming a complex with Ras, B-Raf, and MEK1" 16 : 3562-3573, 2005

32 Dierssen M, "DYRK1A (dualspecificity tyrosine-phosphorylated and -regulated kinase 1A): A Gene with Dosage Effect during Development and Neurogenesis" 6 : 1911-1922, 2006

33 Busciglio J, "Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro.Nature" 378 : 776-779, 1995

34 Kadowaki H, "Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation" 12 : 19-24, 2005

35 Chang HY, "Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx" 281 : 1860-1863, 1998

36 Nishitoh H, "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats" 16 : 1345-1355, 2002

37 Nishitoh H, "ASK1 is essential for JNK/SAPK activation by TRAF2" 242 : 389-395, 1998

38 Gwack Y, "A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT" 441 : 646-650, 2006