Preferred Label : PML Transcription Regulation Pathway;
NCIt synonyms : Transcription Regulation Pathway;
NCIt related terms : Regulation of transcriptional activity by PML;
Alternative definition : BIOCARTA: The PML nuclear bodies are ring-shaped nuclear substructures associated
with the regulation of transcription, transformation, cell growth, and apoptosis and
are characterized by the presence of the protein PML. The activities of PML as a tumor
suppressor and apoptosis inducing factor are exerted through the numerous proteins
it interacts with in the PML-nuclear bodies including the tumor suppressor p53. DNA
damage-induced activation of p53-dependent apoptosis requires PML. PML acts as a coactivator
for p53 and increases acetylation of p53 by the transcriptional coactivator CBP. This
acetylation of p53 is reversed by the deacetylase SirT1, the human homolog of the
yeast gene Sir2, and this deacetylation opposes the transcriptional activation of
p53. The tumor suppressor Rb also interacts with the PML nuclear body, increasing
transcriptional repression of genes involved in cell cycle progression, suggesting
that PML may affect cellular transformation through more than one mechanism. PML interacts
directly with Ubc9, which modifies PML through the attachment of the ubiquitin-like
peptide Sumo-1. Sumo-1 modification of PML is not necessary for the nuclear bodies
to form, but may affect the recruitment of proteins that interact with PML. PML is
involved in non-p53 mediated apoptotic pathways, such as DAXX-mediated apoptosis induced
by Fas and TNF and regulates the transcriptional repressor activity of Daxx. The sequestration
of Daxx by the PML nuclear bodies relieves the repression of other transcription factors
like Pax3 by Daxx. Tumor suppression by PML may in general involve the formation of
specific regulatory transcription complexes, including those with DAXX, p53 and CBP.
Factors that affect the assembly of PML into the PML nuclear bodies affect the proliferation
and transformation of cells. Viral early proteins can interact with PML to disrupt
the nuclear bodies, allowing increased proliferation of cells and reduced apoptosis,
good conditions for DNA virus infection. Another factor that disrupts the formation
of PML nuclear bodies is a translocation between the PML and RAR-alpha genes found
in acute promyelocytic leukemia (APL) patients. Binding of retinoic acid to the RAR-alpha
steroid hormone receptor activates transcription of retinoic-acid responsive genes.
The translocation found in APL patients creates two chimeric proteins, RARalpha-PML
and PML-RARalpha. Retinoic acid given to APL patients causes the reappearance of nuclear
bodies, and the reversal of cellular transformation, affecting a cure for these patients.
(This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_pmlPathway;
Origin ID : C39196;
UMLS CUI : C1519593;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
