Abstract
The YAP1/Hippo and p53 pathways are critical protectors of genome integrity in response to DNA damage. Together, these pathways secure cellular adaptation and maintain overall tissue integrity through transcriptional re-programing downstream of various environmental and biological cues generated during normal tissue growth, cell proliferation, and apoptosis. Genetic perturbations in YAP1/Hippo and p53 pathways are known to contribute to the cells’ ability to turn rogue and initiate tumorigenesis. The Hippo and p53 pathways cooperate on many levels and are closely coordinated through multiple molecular components of their signaling pathways. Several functional and physical interactions have been reported to occur between YAP1/Hippo pathway components and the three p53 family members, p53, p63, and p73. Primarily, functional status of p53 family proteins dictates the subcellular localization, protein stability and transcriptional activity of the core component of the Hippo pathway, Yes-associated protein 1 (YAP1). In this review, we dissect the critical points of crosstalk between the YAP1/Hippo pathway components, with a focus on YAP1, and the p53 tumor suppressor protein family. For each p53 family member, we discuss the biological implications of their interaction with Hippo pathway components in determining cell fate under the conditions of tissue homeostasis and cancer pathogenesis.
Highlights
The Yes-associated protein 1 (YAP1; referred to as YAP), the main effector of the Hippo signaling pathway, has been reported to regulate multiple physiological processes such as tissue regeneration, morphogenesis, metabolism and tumorigenesis as well as a variety of cellular processes spanning cell-cell communication, cell cycle regulation, signal transduction and cytoskeletal remodeling (Zhao et al, 2010; Hansen et al, 2015; Meng et al, 2016; Panciera et al, 2017; Ardestani et al, 2018)
Given the frequent perturbation of YAP/Hippo and p53 pathway activity in human cancer, it is unsurprising that these tumor suppressor pathways are coordinated on multiple levels
Crosstalk between the p53 family members and YAP can either elicit tumor suppressor or oncogenic effects depending on the functional status and available ratios of p53 protein family
Summary
The Yes-associated protein 1 (YAP1; referred to as YAP), the main effector of the Hippo signaling pathway, has been reported to regulate multiple physiological processes such as tissue regeneration, morphogenesis, metabolism and tumorigenesis as well as a variety of cellular processes spanning cell-cell communication, cell cycle regulation, signal transduction and cytoskeletal remodeling (Zhao et al, 2010; Hansen et al, 2015; Meng et al, 2016; Panciera et al, 2017; Ardestani et al, 2018). YAP has been reported to function as a tumor suppressor in breast cancer and hematological malignancies by promoting apoptosis in these contexts.
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