The human orthologue of Drosophila ecdysoneless protein interacts with p53 and regulates its function.
Biochemical mechanisms that control the levels and function of key tumor suppressor proteins are of great interest as their alterations can lead to oncogenic transformation. Here, we identify the human orthologue of Drosophila melanogaster ecdysoneless (hEcd) as a novel p53-interacting protein. Overexpression of hEcd increases the levels of p53 and enhances p53 target gene transcription whereas hEcd knockdown has the opposite effects on p53 levels and target gene expression. Furthermore, hEcd interacts with murine double minute-2 and stabilizes p53 by inhibiting murine double minute-2-mediated degradation of p53. Thus, hEcd protein represents a novel regulator of p53 stability and function. Our studies also represent the first demonstration of a biochemical function for hEcd protein and raise the possibility that altered hEcd levels and/or function may contribute to oncogenesis.
Zhang
Ying
Y
Division of Cancer Biology and Molecular Oncology, Department of Medicine, Evanston Northwestern Healthcare Research Institute and Feinberg School of Medicine, and Robert H. Lurie Comprehensive Cancer Center, Evanston, Illinois 60201, USA.
Chen
Jianming
J
Gurumurthy
Channabasavaiah B
CB
Kim
Junhyun
J
Bhat
Ishfaq
I
Gao
Qingshen
Q
Dimri
Goberdhan
G
Lee
Sam W
SW
Band
Hamid
H
Band
Vimla
V
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D051379:Mice; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C513410:ECD protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2