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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

(A) The Drosophila Hippo pathway. Signaling diagram of Hippo (Hpo) kinases cascade and of its modulation by apical transmembrane protein complexes and proteins involved in cell polarity control (Arrowed or blunted ends indicate activation or inhibition, respectively). (B) Role of YAP in the Hpo-like pathway in human. In mammals the relationships between Drosophila Hpo and Wts, are conserved in Mst1/2 (Hpo homologs) and Lats1/2 (Wts homolog). Lats1/2 phosphorylates YAP on different conserved motifs. Phosphorylation-dependent 14-3-3 binding and cytoplasmic retention are conserved in YAP, which inhibits it to enhance the transcriptional activation of pro-proliferation genes. Depending on the cellular context Lats1/2 phosphorylates YAP, increasing its transcriptional support to p73 to induce apoptosis. YAP can also be phosphorylated by other kinase, such as CDK1δ/ε promoting its subsequent protein proteasome-degradation. The retention of YAP at cytoplasmic level can also be exerted by sequestering the protein at the junctional level through the interaction with the AMOT protein.
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Figure 1: (A) The Drosophila Hippo pathway. Signaling diagram of Hippo (Hpo) kinases cascade and of its modulation by apical transmembrane protein complexes and proteins involved in cell polarity control (Arrowed or blunted ends indicate activation or inhibition, respectively). (B) Role of YAP in the Hpo-like pathway in human. In mammals the relationships between Drosophila Hpo and Wts, are conserved in Mst1/2 (Hpo homologs) and Lats1/2 (Wts homolog). Lats1/2 phosphorylates YAP on different conserved motifs. Phosphorylation-dependent 14-3-3 binding and cytoplasmic retention are conserved in YAP, which inhibits it to enhance the transcriptional activation of pro-proliferation genes. Depending on the cellular context Lats1/2 phosphorylates YAP, increasing its transcriptional support to p73 to induce apoptosis. YAP can also be phosphorylated by other kinase, such as CDK1δ/ε promoting its subsequent protein proteasome-degradation. The retention of YAP at cytoplasmic level can also be exerted by sequestering the protein at the junctional level through the interaction with the AMOT protein.

Mentions: First identified in Drosophila, the Hippo (Hpo) signaling pathway is a conserved string of molecular events, which regulates the proper size of organs through the balance of cell growth and cell death. Cell density and contact inhibition information are conveyed by membrane complexes through the Hpo pathway to specific transcriptional programs in the nucleus. In contact-inhibited cells, the Hpo pathway is activated, whereas in sparsely populated cells, it is inhibited. The pathway is characterized by a core kinase, Hpo (Mst1 and Mst2 in mammals), and its downstream effector, Warts (Wts) kinase (Lats1 and Lats2 in mammals), which regulate Yorkie (Yki), protein (YAP and TAZ in mammals), a transcriptional co-activator for transcription factors involved in the induction of cell proliferation, survival, and apoptosis (Figures 1A,B).


PML Surfs into HIPPO Tumor Suppressor Pathway.

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

(A) The Drosophila Hippo pathway. Signaling diagram of Hippo (Hpo) kinases cascade and of its modulation by apical transmembrane protein complexes and proteins involved in cell polarity control (Arrowed or blunted ends indicate activation or inhibition, respectively). (B) Role of YAP in the Hpo-like pathway in human. In mammals the relationships between Drosophila Hpo and Wts, are conserved in Mst1/2 (Hpo homologs) and Lats1/2 (Wts homolog). Lats1/2 phosphorylates YAP on different conserved motifs. Phosphorylation-dependent 14-3-3 binding and cytoplasmic retention are conserved in YAP, which inhibits it to enhance the transcriptional activation of pro-proliferation genes. Depending on the cellular context Lats1/2 phosphorylates YAP, increasing its transcriptional support to p73 to induce apoptosis. YAP can also be phosphorylated by other kinase, such as CDK1δ/ε promoting its subsequent protein proteasome-degradation. The retention of YAP at cytoplasmic level can also be exerted by sequestering the protein at the junctional level through the interaction with the AMOT protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: (A) The Drosophila Hippo pathway. Signaling diagram of Hippo (Hpo) kinases cascade and of its modulation by apical transmembrane protein complexes and proteins involved in cell polarity control (Arrowed or blunted ends indicate activation or inhibition, respectively). (B) Role of YAP in the Hpo-like pathway in human. In mammals the relationships between Drosophila Hpo and Wts, are conserved in Mst1/2 (Hpo homologs) and Lats1/2 (Wts homolog). Lats1/2 phosphorylates YAP on different conserved motifs. Phosphorylation-dependent 14-3-3 binding and cytoplasmic retention are conserved in YAP, which inhibits it to enhance the transcriptional activation of pro-proliferation genes. Depending on the cellular context Lats1/2 phosphorylates YAP, increasing its transcriptional support to p73 to induce apoptosis. YAP can also be phosphorylated by other kinase, such as CDK1δ/ε promoting its subsequent protein proteasome-degradation. The retention of YAP at cytoplasmic level can also be exerted by sequestering the protein at the junctional level through the interaction with the AMOT protein.
Mentions: First identified in Drosophila, the Hippo (Hpo) signaling pathway is a conserved string of molecular events, which regulates the proper size of organs through the balance of cell growth and cell death. Cell density and contact inhibition information are conveyed by membrane complexes through the Hpo pathway to specific transcriptional programs in the nucleus. In contact-inhibited cells, the Hpo pathway is activated, whereas in sparsely populated cells, it is inhibited. The pathway is characterized by a core kinase, Hpo (Mst1 and Mst2 in mammals), and its downstream effector, Warts (Wts) kinase (Lats1 and Lats2 in mammals), which regulate Yorkie (Yki), protein (YAP and TAZ in mammals), a transcriptional co-activator for transcription factors involved in the induction of cell proliferation, survival, and apoptosis (Figures 1A,B).

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