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	PRAK Suppresses Oncogenic ras-Induced Hematopoietic Cancer Development by Antagonizing the JNK Pathway
	Yoshizuka, Naoto ; Lai, Maoyi ; Liao, Rong ; Cook, Ryan ; Xiao, Changchun ; Han, Jiahuai ; Han JH(韩家淮) ; Sun, Peiqing
	2012-06
关键词	C-JUN CELL-PROLIFERATION INDUCED SENESCENCE MAP KINASE TUMOR SUPPRESSION MAMMALIAN-CELLS P38 P53 DIFFERENTIATION TUMORIGENESIS
英文摘要	The p38 mitogen-activated protein kinase (MAPK) pathway regulates multiple physiologic and pathologic processes, including cancer development. PRAK, a p38 substrate protein kinase, has previously been implicated in the suppression of skin carcinogenesis. In the current study, we show that PRAK deletion accelerates hematopoietic cancer development in a mouse model harboring an oncogenic ras allele, E mu-N-Ras(G12D), specifically expressed in hematopoietic cells. Further investigation reveals that enhanced hematopoietic tumorigenesis by PRAK deficiency is associated with hyperactivation of the c-jun-NH2-kinase (JNK) pathway both in vivo and in primary hematopoietic cells isolated from spleens. In primary splenocytes, PRAK deficiency further enhanced oncogenic ras-induced cell proliferation and promoted ras-mediated colony formation on semisolid medium in a JNK-dependent manner. In addition, deletion of PRAK leads to abrogation of ras-induced accumulation of senescence markers. These findings indicate that PRAK suppresses hematopoietic cancer formation in this mouse model by antagonizing oncogenic ras-induced activation of the JNK pathway. Our results suggest that PRAK may function as a tumor suppressor in multiple types of cancers. Mol Cancer Res; 10(6); 810-20. (C) 2012 AACR.; NIH [CA106768, CA131231, RR025744]; NSF China [30828019]
语种	英语
出版者	AMER ASSOC CANCER RESEARCH
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1158/1541-7786.MCR-11-0576]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Yoshizuka, Naoto,Lai, Maoyi,Liao, Rong,et al. PRAK Suppresses Oncogenic ras-Induced Hematopoietic Cancer Development by Antagonizing the JNK Pathway[J],2012.
APA	Yoshizuka, Naoto.,Lai, Maoyi.,Liao, Rong.,Cook, Ryan.,Xiao, Changchun.,...&Sun, Peiqing.(2012).PRAK Suppresses Oncogenic ras-Induced Hematopoietic Cancer Development by Antagonizing the JNK Pathway..
MLA	Yoshizuka, Naoto,et al."PRAK Suppresses Oncogenic ras-Induced Hematopoietic Cancer Development by Antagonizing the JNK Pathway".(2012).

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