The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network

Lindsey Mayo, David B. Donner

Research output: Contribution to journalArticle

298 Citations (Scopus)

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

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Tumor Suppressor Proteins
Oncogene Proteins
Tumors
Tumor Suppressor Protein p53
Neoplasms
Phosphorylation
Chemotherapy
Cell growth
Phosphatidylinositols
Phosphatidylinositol 3-Kinases
Cytoplasm
PTEN Phosphohydrolase
Repair
Chemical activation
Cells
1-Phosphatidylinositol 4-Kinase
Cell Survival
Down-Regulation
Drug Therapy
Growth

ASJC Scopus subject areas

  • Biochemistry

Cite this

The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. / Mayo, Lindsey; Donner, David B.

In: Trends in Biochemical Sciences, Vol. 27, No. 9, 01.09.2002, p. 462-467.

Research output: Contribution to journalArticle

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