Details

Autor(en) / Beteiligte

• Vallian, Sadeq
• Gäken, Joop A.
• Trayner, Ian D.
• Gingold, Elliot B.
• Kouzarides, Tony
• Chang, Kun-Sang
• Farzaneh, Farzin

Titel

Transcriptional Repression by the Promyelocytic Leukemia Protein, PML

Ist Teil von

• Experimental cell research, 1997-12, Vol.237 (2), p.371-382

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1997

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Acute promyelocytic leukemia is characterized by the presence of a t(15;17) chromosomal translocation which results in the expression of a chimeric gene product, PMLRARα, consisting of an N-terminal-truncated retinoic acid receptor-α fused to a C-terminal-truncated PML. Several structural features, and regions of homology to known transcription factors, suggest that PML may be involved in the regulation of gene expression. In this study we have analyzed the transcriptional regulatory activity of PML using chimeric GAL4/PML constructs and GAL4-responsive reporter plasmids. The data presented demonstrate that PML, when fused to the DNA-binding domain of GAL4 (GAL4/PML), inhibits transcription from GAL4-responsive promoters. The magnitude of this repression is cell type and promoter dependent, and deletion studies show that the putative coiled-coil and part of the serine-rich regions of PML are required for this activity. These regions are also shown to be responsible for the repression of transcription activity from the EGFR promoter. The data presented also demonstrate that GAL4/PML can recruit PMLRARα resulting in the retinoid-inducible transcriptional activation of a GAL4-responsive promoter, a function dependent on the presence of the coiled-coil region of PMLRARα.