MVP interacts with YPEL4 and inhibits YPEL4-mediated activities of the ERK signal pathway
MVP interacts with YPEL4 and inhibits YPEL4-mediated activities of the ERK signal pathway
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MVP 与 YPEL4 相互作用并抑制 YPEL4 介导的 ERK 信号通路活性
DOI：
10.1139/o09-166
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发表时间：
2010-06-01
影响因子：
2.9
通讯作者：
Wu, Xiushan
中科院分区：
文献类型：
--
作者：
Liang, Pei;Wan, Yongqi;Wu, Xiushan
人YPEL 4是YPEL家族的成员。它包含一个Yippee结构域，这是一个假定的锌指样金属结合结构域。人YPEL 4基因定位于染色体11q12.1，在成人组织中广泛表达。并编码一个127个氨基酸的核蛋白，其功能尚不清楚。为了深入了解这种蛋白质的细胞功能，我们使用酵母双杂交筛选搜索YPEL 4相互作用蛋白。肺耐药相关蛋白主要穹窿蛋白（MVP）被鉴定为YPEL 4的结合伴侣。通过哺乳动物双杂交、GST pull-down、免疫共沉淀和免疫细胞化学等一系列生物化学试验进一步证实了YPEL 4与MVP在哺乳动物细胞中的相互作用。使用报告系统，我们发现MVP可以抑制YPEL 4在MAPK信号通路中激活Elk-1的能力。本研究为深入了解YPEL 4在细胞分裂和信号转导通路中的分子机制提供了新的线索，有助于进一步了解YPEL家族的分子功能。
Human YPEL4 is a member of YPEL family. It contains a Yippee domain, which is a putative zinc-finger-like, metal-binding domain. The human YPEL4 gene maps to chromosome 11q12.1, is ubiquitously expressed in adult tissues. and encodes a nuclear protein of 127 amino acids, the function of which remains unknown. To gain insights into the cellular function of this protein, we searched for YPEL4-interacting proteins using a yeast two-hybrid screen. The major vault protein (MVP), a lung resistance associated protein, was identified as a binding partner of YPEL4. The interaction between YPEL4 and MVP in mammalian cells was further demonstrated by a series of biochemical assays including the mammalian two-hybrid assay, GST pull-down assay, co-immunoprecipitation assay, and immunocytochemistry. Using a reporter system, we found that MVP can inhibit YPEL4's ability to activate Elk-1 in the MAPK signaling pathway. This study provides new clues for understanding the molecular mechanism of YPEL4 in cell division and signal transduction pathways and should be helpful for understanding molecular functions of the YPEL family.