MVP interacts with YPEL4 and inhibits YPEL4-mediated activities of the ERK signal pathway.
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.
Liang
Pei
P
The Center for Heart Development, Key Laboratory of MOE for Developmental Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, People's Republic of China.
Wan
Yongqi
Y
Yan
Yan
Y
Wang
Yuequn
Y
Luo
Na
N
Deng
Yun
Y
Fan
Xiongwei
X
Zhou
Junmei
J
Li
Yongqing
Y
Wang
Zequn
Z
Yuan
Wuzhou
W
Tang
Ming
M
Mo
Xiaoyang
X
Wu
Xiushan
X
D015153:Blotting, Western; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D016335:Zinc Fingers; D000099187:Major Vault Protein
D002352:Carrier Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C551886:YPEL4 protein, human