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

Research output: Contribution to journalArticle

162 Citations (Scopus)

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

Fingerprint

Aptitude
Growth
Co-Repressor Proteins
Neoplasms
Chromosomes, Human, Pair 10
Oncogene Proteins
Tumor Suppressor Genes
Carcinogens
Prostatic Neoplasms
Carcinogenesis
Adenocarcinoma
Homeostasis
Epithelium
Binding Sites
Maintenance
Phenotype
Mutation
DNA
Proteins
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Schreiber-Agus, N., Meng, Y., Hoang, T., Hou, H., Ghen, K., Greenberg, R., ... 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

Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth. / Schreiber-Agus, Nicole; Meng, Yong; Hoang, Tin; Hou, Harry; Ghen, Ken; Greenberg, Roger; Cordon-Cardo, Carlos; Leet, Han Woong; Depinho, Ronald A.

In: Nature, Vol. 393, No. 6684, 04.06.1998, p. 483-487.

Research output: Contribution to journalArticle

Schreiber-Agus, N, Meng, Y, Hoang, T, Hou, H, Ghen, K, Greenberg, R, Cordon-Cardo, C, Leet, HW & Depinho, RA 1998, 'Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth', Nature, vol. 393, no. 6684, pp. 483-487. https://doi.org/10.1038/31008
Schreiber-Agus N, Meng Y, Hoang T, Hou H, Ghen K, Greenberg R et al. Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth. Nature. 1998 Jun 4;393(6684):483-487. https://doi.org/10.1038/31008
Schreiber-Agus, Nicole ; Meng, Yong ; Hoang, Tin ; Hou, Harry ; Ghen, Ken ; Greenberg, Roger ; Cordon-Cardo, Carlos ; Leet, Han Woong ; Depinho, Ronald A. / Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth. In: Nature. 1998 ; Vol. 393, No. 6684. pp. 483-487.
@article{dd95613cea144fb5b4309e5b12db1be6,
title = "Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth",
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.",
author = "Nicole Schreiber-Agus and Yong Meng and Tin Hoang and Harry Hou and Ken Ghen and Roger Greenberg and Carlos Cordon-Cardo and Leet, {Han Woong} and Depinho, {Ronald A.}",
year = "1998",
month = "6",
day = "4",
doi = "10.1038/31008",
language = "English (US)",
volume = "393",
pages = "483--487",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6684",

}

TY - JOUR

T1 - Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth

AU - Schreiber-Agus, Nicole

AU - Meng, Yong

AU - Hoang, Tin

AU - Hou, Harry

AU - Ghen, Ken

AU - Greenberg, Roger

AU - Cordon-Cardo, Carlos

AU - Leet, Han Woong

AU - Depinho, Ronald A.

PY - 1998/6/4

Y1 - 1998/6/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032482421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032482421&partnerID=8YFLogxK

U2 - 10.1038/31008

DO - 10.1038/31008

M3 - Article

C2 - 9624006

AN - SCOPUS:0032482421

VL - 393

SP - 483

EP - 487

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6684

ER -