Role of PML in cell growth and the retinoic acid pathway

Zhu Gang Wang, Laurent Delva, Mirella Gaboli, Roberta Rivi, Marco Giorgio, Carlos Cordon-Cardo, Frank Grosveld, Pier Paolo Pandolfi

Research output: Contribution to journalArticlepeer-review

464 Scopus citations

Abstract

The PML gene is fused to the retinoic acid receptor α (RARα) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL). Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorigenesis. PML was essential for the tumor-growth-suppressive activity of retinoic acid (RA) and for its ability to induce terminal myeloid differentiation of precursor cells. PML was needed for the RA-dependent transactivation of the p21(WAF1/GIP1 gene, which regulates cell cycle progression and cellular differentiation. These results indicate that PML is a critical component of the RA pathway and that disruption of its activity by the PML-RARα fusion protein may be important in an APL pathogenesis.

Original languageEnglish
Pages (from-to)1547-1551
Number of pages5
JournalScience
Volume279
Issue number5356
DOIs
StatePublished - 6 Mar 1998
Externally publishedYes

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