BIOMEDICINE: A Supporting Role in Tumor Suppression

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Science  16 Nov 2001:
Vol. 294, Issue 5546, pp. 1421b
DOI: 10.1126/science.294.5546.1421b

The signaling pathways that regulate cell growth are themselves subject to regulation, and there is great interest in identifying the factors that control the activity of these pathways in vivo.

To investigate the regulation of the p53-Mdm2-Arf tumor suppressor pathway, Inoue et al. studied mice deficient in Dmp1, a nuclear phosphoprotein that transcriptionally activates the Arf gene. In their second year of life, mice lacking one or both copies of the Dmp1 gene spontaneously developed tumors in many different tissues. Dmp1 loss accelerated tumorigenesis in a mouse lymphoma model, and the resultant tumors were notably devoid of mutations in p53 and Arf, suggesting that Dmp1 is a potent modifier of the p53-Mdm2-Arf pathway. It is possible that the minor subset of human tumors that show no evidence of mutation in p53 or Arf may, in fact, have mutations in the genes encoding key regulatory factors such as Dmp, producing the same disruptive effect on cell growth control.—PAK

Genes Dev., in press.

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