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PML Surfs into HIPPO Tumor Suppressor Pathway.

Strano S, Fausti F, Di Agostino S, Sudol M, Blandino G - Front Oncol (2013)

Bottom Line: Growth arrest, inhibition of cell proliferation, apoptosis, senescence, and differentiation are the most characterized effects of a given tumor suppressor response.The latter may happen through the concomitant involvement of common nodal proteins.PML, in addition to its own anti-tumor activity, contributes to the assembly of an integrated and superior network that may be necessary for the maximization of the tumor suppressor response to diverse oncogenic insults.

View Article: PubMed Central - PubMed

Affiliation: Molecular Chemoprevention Group, Molecular Medicine Area, Regina Elena National Cancer Institute Rome, Italy.

ABSTRACT
Growth arrest, inhibition of cell proliferation, apoptosis, senescence, and differentiation are the most characterized effects of a given tumor suppressor response. It is becoming increasingly clear that tumor suppression results from the integrated and synergistic activities of different pathways. This implies that tumor suppression includes linear, as well as lateral, crosstalk signaling. The latter may happen through the concomitant involvement of common nodal proteins. Here, we discuss the role of Promyelocytic leukemia protein (PML) in functional cross-talks with the HIPPO and the p53 family tumor suppressor pathways. PML, in addition to its own anti-tumor activity, contributes to the assembly of an integrated and superior network that may be necessary for the maximization of the tumor suppressor response to diverse oncogenic insults.

No MeSH data available.


Related in: MedlinePlus

Involvement of YAP in the DNA damage response. Schematic representation of the DNA damage response induced by Cisplatin (CDDP) treatment. It was shown to signal c-Abl-mediated YAP phosphorylation, resulting in YAP nuclear localization and increased p73 binding and activation of pro-apoptotic genes. By contrast, active Akt counters this effect by phosphorylating YAP and sequestering it at the cytoplasmic level.
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Figure 2: Involvement of YAP in the DNA damage response. Schematic representation of the DNA damage response induced by Cisplatin (CDDP) treatment. It was shown to signal c-Abl-mediated YAP phosphorylation, resulting in YAP nuclear localization and increased p73 binding and activation of pro-apoptotic genes. By contrast, active Akt counters this effect by phosphorylating YAP and sequestering it at the cytoplasmic level.

Mentions: p53 protein is known as the “guardian of the genome” and is the focus of studies in understanding tumorigenesis. Another member of the p53 family, p73, was recently discovered for its pivotal role in DNA damage signaling. The main activities of the p53 family occur through the transcriptional activation or repression of target genes that encode key proteins involved in cell growth inhibition, apoptosis, senescence, and differentiation (Vousden and Lu, 2002). However, the members of the family differ in their upstream regulation by different kinases. The YAP is a critical mediator of p73 function. It binds p73 to regulate its transcriptional activity (Strano et al., 2001) and subsequent cell death induction (Basu et al., 2003). This binding is negatively regulated by Akt-mediated YAP phosphorylation (Basu et al., 2003; Figure 2) and enhanced by DNA damage (Strano et al., 2005). Furthermore, YAP stabilizes p73 protein in a post-translational way by competing with the ITCH E3-ligase for binding to p73 (Levy et al., 2007) and inducing its transcriptional activity via the p300 acteyltansferase (Strano et al., 2005). Rossi et al. (2005) have shown that Itch, a human ubiquitin protein ligase that belongs to the Nedd4-like E3 family containing a WW domain, binds, and ubiquitinates p73 and determines its rapid proteosome-dependent degradation.


PML Surfs into HIPPO Tumor Suppressor Pathway.

Strano S, Fausti F, Di Agostino S, Sudol M, Blandino G - Front Oncol (2013)

Involvement of YAP in the DNA damage response. Schematic representation of the DNA damage response induced by Cisplatin (CDDP) treatment. It was shown to signal c-Abl-mediated YAP phosphorylation, resulting in YAP nuclear localization and increased p73 binding and activation of pro-apoptotic genes. By contrast, active Akt counters this effect by phosphorylating YAP and sequestering it at the cytoplasmic level.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585432&req=5

Figure 2: Involvement of YAP in the DNA damage response. Schematic representation of the DNA damage response induced by Cisplatin (CDDP) treatment. It was shown to signal c-Abl-mediated YAP phosphorylation, resulting in YAP nuclear localization and increased p73 binding and activation of pro-apoptotic genes. By contrast, active Akt counters this effect by phosphorylating YAP and sequestering it at the cytoplasmic level.
Mentions: p53 protein is known as the “guardian of the genome” and is the focus of studies in understanding tumorigenesis. Another member of the p53 family, p73, was recently discovered for its pivotal role in DNA damage signaling. The main activities of the p53 family occur through the transcriptional activation or repression of target genes that encode key proteins involved in cell growth inhibition, apoptosis, senescence, and differentiation (Vousden and Lu, 2002). However, the members of the family differ in their upstream regulation by different kinases. The YAP is a critical mediator of p73 function. It binds p73 to regulate its transcriptional activity (Strano et al., 2001) and subsequent cell death induction (Basu et al., 2003). This binding is negatively regulated by Akt-mediated YAP phosphorylation (Basu et al., 2003; Figure 2) and enhanced by DNA damage (Strano et al., 2005). Furthermore, YAP stabilizes p73 protein in a post-translational way by competing with the ITCH E3-ligase for binding to p73 (Levy et al., 2007) and inducing its transcriptional activity via the p300 acteyltansferase (Strano et al., 2005). Rossi et al. (2005) have shown that Itch, a human ubiquitin protein ligase that belongs to the Nedd4-like E3 family containing a WW domain, binds, and ubiquitinates p73 and determines its rapid proteosome-dependent degradation.

Bottom Line: Growth arrest, inhibition of cell proliferation, apoptosis, senescence, and differentiation are the most characterized effects of a given tumor suppressor response.The latter may happen through the concomitant involvement of common nodal proteins.PML, in addition to its own anti-tumor activity, contributes to the assembly of an integrated and superior network that may be necessary for the maximization of the tumor suppressor response to diverse oncogenic insults.

View Article: PubMed Central - PubMed

Affiliation: Molecular Chemoprevention Group, Molecular Medicine Area, Regina Elena National Cancer Institute Rome, Italy.

ABSTRACT
Growth arrest, inhibition of cell proliferation, apoptosis, senescence, and differentiation are the most characterized effects of a given tumor suppressor response. It is becoming increasingly clear that tumor suppression results from the integrated and synergistic activities of different pathways. This implies that tumor suppression includes linear, as well as lateral, crosstalk signaling. The latter may happen through the concomitant involvement of common nodal proteins. Here, we discuss the role of Promyelocytic leukemia protein (PML) in functional cross-talks with the HIPPO and the p53 family tumor suppressor pathways. PML, in addition to its own anti-tumor activity, contributes to the assembly of an integrated and superior network that may be necessary for the maximization of the tumor suppressor response to diverse oncogenic insults.

No MeSH data available.


Related in: MedlinePlus