DAF-5 is a Ski oncoprotein homolog that functions in a neuronal TGFβ pathway to regulate C. elegans dauer development

被引:71
作者
da Graca, LS
Zimmerman, KK
Mitchell, MC
Kozhan-Gorodetska, M
Sekiewicz, K
Morales, Y
Patterson, GI [1 ]
机构
[1] Rutgers State Univ, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA
[2] Canc Inst New Jersey, New Brunswick, NJ 08853 USA
来源
DEVELOPMENT | 2004年 / 131卷 / 02期
关键词
dauer; cyclin dependent kinase inhibitor; dachshund box; nematode;
D O I
10.1242/dev.00922
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
An unconventional TGFbeta superfamily pathway plays a crucial role in the decision between dauer diapause and reproductive growth. We have studied the daf-5 gene, which, along with the daf-3 Smad gene, is antagonized by upstream receptors and receptor-regulated Smads. We show that DAF-5 is a novel member of the Sno/Ski superfamily that binds to DAF-3 Smad, suggesting that DAF-5, like Sno/Ski, is a regulator of transcription in a TGFbeta superfamily signaling pathway. However, we present evidence that DAF-5 is an unconventional Sno/Ski protein, because DAF-5 acts as a co-factor, rather than an antagonist, of a Smad protein. We show that expressing DAF-5 in the nervous system rescues a daf-5 mutant, whereas muscle or hypodermal expression does not. Previous work suggested that DAF-5 and DAF-3 function in pharyngeal muscle to regulate gene expression, but our analysis of regulation of a pharynx specific promoter suggests otherwise. We present a model in which DAF-5 and DAF-3 control the production or release of a hormone from the nervous system by either regulating the expression of biosynthetic genes or by altering the connectivity or the differentiated state of neurons.
引用
收藏
页码:435 / 446
页数:12
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