p53-independent functions of the p19ARF tumor suppressor

Author:

Weber Jason D.,Jeffers John R.,Rehg Jerold E.,Randle David H.,Lozano Guillermina,Roussel Martine F.,Sherr Charles J.,Zambetti Gerard P.

Abstract

The p19ARF tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53and Mdm2 or p53 alone, demonstrating that p19ARF can act independently of the Mdm2-p53 axis in tumor surveillance. Reintroduction of ARF into TKO mouse embryo fibroblasts (MEFs), but not into those lacking both p53 andARF, arrested the cell division cycle in the G1 phase. Inhibition of the retinoblastoma protein had no effect on the ability of ARF to arrest TKO MEFs. Thus, in the absence of Mdm2, p19ARF interacts with other targets to inhibit cell proliferation.

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

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