Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth

Nicole Schreiber-Agus, Yong Meng, Tin Hoang, Harry Hou, Ken Ghen, Roger Greenberg, Carlos Cordon-Cardo, Han Woong Leet, Ronald A. Depinho

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162 Scopus citations

Abstract

Mxi1 belongs to the Mad (Mxi1) family of patients, which function as potent antagonists of Myc oncoproteins. This antagonism relates partly to their ability to compete with Myc for the protein Max and for consensus DNA binding sites and to recruit transcriptional co-repressors. Mad(Mxi1) proteins have been suggested to be essential in cellular growth control and/or in the induction and maintenance of the differentiated state. Consistent with these roles, mxi1 may be the tumour-suppressor gene that resides at region 24-26 of the long arm of chromosome 10. This region is a cancer hotspot, and mutations here may be involved in several cancers, including prostate adenocarcinoma. Here we show that mice lacking Mxi1 exhibitor progressive, multisystem abnormalities. These mice also show increased susceptibility to tumorigenesis either following carcinogen treatment or when also deficient in Ink4a. This cancer-prone phenotype may correlate with the enhanced ability of several mxi1-deficient cell types, including prostatic epithelium, to proliferate. Our results show that Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner.

Original languageEnglish (US)
Pages (from-to)483-487
Number of pages5
JournalNature
Volume393
Issue number6684
DOIs
StatePublished - Jun 4 1998
Externally publishedYes

ASJC Scopus subject areas

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    Schreiber-Agus, N., Meng, Y., Hoang, T., Hou, H., Ghen, K., Greenberg, R., Cordon-Cardo, C., Leet, H. W., & Depinho, R. A. (1998). Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth. Nature, 393(6684), 483-487. https://doi.org/10.1038/31008