The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network

Lindsey D. Mayo, David B. Donner

Research output: Contribution to journalReview article

310 Scopus citations

Abstract

Oncoproteins and tumor-suppressor proteins regulate cell growth and viability. Recent observations show that phosphoinositide 3-kinase (PtdIns 3-kinase)-Akt signaling promotes the phosphorylation and movement of the Mdm2 oncoprotein into the nucleus, where it downregulates the p53 tumor-suppressor protein. The PTEN tumor suppressor protein inhibits activation of Akt and this restricts Mdm2 to the cytoplasm. Restriction of Mdm2 to the cytoplasm promotes p53 function and thereby sustains the sensitivity of cancer cells to chemotherapy. p53 acutely induces Mdm2, providing damaged cells the opportunity for repair, but subsequently induces PTEN, favoring the death of mutated or irrevocably damaged cells. Thus, oncoproteins and tumor suppressor proteins are networked to promote normal cell function and eliminate mutated cells.

Original languageEnglish (US)
Pages (from-to)462-467
Number of pages6
JournalTrends in Biochemical Sciences
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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