p53 shades of Hippo

The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar...

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Bibliographic Details
Published in:Cell death and differentiation 2018-01, Vol.25 (1), p.81-92
Main Authors: Furth, Noa, Aylon, Yael, Oren, Moshe
Format: Article
Language:English
Subjects:
631/67/1244
631/67/395
Animals
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cancer
Carcinogenesis
Cell Biology
Cell cycle
Cell Cycle Analysis
Cellular Senescence
Epigenetics
Genomic instability
Humans
Kinases
Life Sciences
Metabolism
Neoplastic Stem Cells - metabolism
p53 Protein
Ploidies
Protein-Serine-Threonine Kinases - metabolism
Review
Senescence
Shades
Signal Transduction
Stem Cells
Stem Cells - metabolism
Transcription
Transcription Factors - metabolism
Transformed cells
Tumor suppression
Tumor Suppressor Protein p53 - metabolism
Yes-associated protein
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Summary:The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ. A wealth of accumulated data suggests a complex and delicate regulatory network connecting the p53 and Hippo pathways, in a highly context-specific manner. This generates multiple layers of interaction, ranging from interdependent and collaborative signaling to apparent antagonistic activity. Furthermore, genetic and epigenetic alterations can disrupt this homeostatic network, paving the way to genomic instability and cancer. This strengthens the need to better understand the nuances that control the molecular function of each component and the cross-talk between the different components. Here, we review interactions between the p53 and Hippo pathways within a subset of physiological contexts, focusing on normal stem cells and development, as well as regulation of apoptosis, senescence and metabolism in transformed cells.
ISSN:1350-9047
1476-5403
DOI:10.1038/cdd.2017.163