YAP and TAZ Are Not Identical Twins

Reggiani, Francesca; Gobbi, Giulia; Ciarrocchi, Alessia; Sancisi, Valentina

doi:10.1016/j.tibs.2020.08.012

Cited by 101 publications

(111 citation statements)

References 95 publications

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“…extracellular rigidity (Dupont et al 2011;Dupont 2016;Pocaterra et al 2020). Although TAZ and YAP are paralogs with functional redundancy and tumor-promoting effects (Kim 2019), it is clear that TAZ and YAP play distinctively essential roles in normal tissue development and homeostasis (Yu et al 2015;Reggiani et al 2020). We clarify the The essential role of TAZ in normal tissue homeostasis genetic and protein structural features of TAZ and further highlight its biological functions in normal tissue differentiation from stem cells and in the regulation of tissue homeostasis.…”

Section: Introductionmentioning

confidence: 88%

“…Many transcription factors, including Runt-related transcription factors (RUNXs), peroxisome proliferator-activated receptor γ (PPARγ), TEADs, SMADs, ErbB-4, and p73 are known to interact with the WW domain in TAZ or YAP (Strano et al 2001;Ferrigno et al 2002;Komuro et al 2003;Zhao et al 2009). Since TAZ contains a single WW domain unlike two WW domains in YAP, its interaction with TEAD is structurally different from TEAD-YAP (Kaan et al 2017;Reggiani et al 2020). TAZ can be distinguished from YAP by its interactions with many P-rich proteins and functions within the cells.…”

Section: Structural Features Of Tazmentioning

confidence: 99%

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The essential role of TAZ in normal tissue homeostasis

2021

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Transcriptional coactivator with PDZ-binding motif (TAZ) has been extensively characterized in organ development, tissue regeneration, and tumor progression. In particular, TAZ functions as a Hippo mediator that regulates organ size, tumor growth and migration. It is highly expressed in various types of human cancer, and has been reported to be associated with tumor metastasis and poor outcomes in cancer patients, suggesting that TAZ is an oncogenic regulator. Yes-associated protein (YAP) has 60% similarity in amino acid sequence to TAZ and plays redundant roles with TAZ in the regulation of cell proliferation and migration of cancer cells. Therefore, TAZ and YAP, which are encoded by paralogous genes, are referred to as TAZ/YAP and are suggested to be functionally equivalent. Despite its similarity to YAP, TAZ can be clearly distinguished from YAP based on its genetic, structural, and functional aspects. In addition, targeting superabundant TAZ can be a promising therapeutic strategy for cancer treatment; however, persistent TAZ inactivation may cause failure of tissue homeostatic control. This review focuses primarily on TAZ, not YAP, discusses its structural features and physiological functions in the regulation of tissue homeostasis, and provides new insights into the drug development targeting TAZ to control reproductive and musculoskeletal disorders.

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Section: Introductionmentioning

confidence: 88%

Section: Structural Features Of Tazmentioning

confidence: 99%

The essential role of TAZ in normal tissue homeostasis

2021

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“…Contextual dissection of YAP and TAZ (both as individual proteins and comparing them as paralogs) is key, because prior literature has shown many conflicting roles for these proteins in cell fate changes, both in self-renewal vs. differentiation and survival vs. cell death [21], whereas other processes like cell motility and regulation by the cytoskeleton seem to show more consensus. It also remains controversial whether they are functionally redundant or fulfill unique roles [22]. Stem cells and cancer are relevant systems for this undertaking, as they share capacity for differentiation and self-renewal as well as similar signaling pathways [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

LeBlanc

Ramirez

Kim

2021

Cell. Mol. Life Sci.

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Hippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.

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“…[1][2][3][4][5] The main function of the Hippo pathway is to negatively regulate the activity of the transcription coactivator Yes-associated protein 1 (YAP, encoded by YAP1) and its paralog, transcriptional coactivator with PDZ-binding motif (TAZ, encoded by WWTR1) (Figure 1). YAP and TAZ have many similarities in their structures, functions and regulations, yet they are not completely redundant ( 6,7 ; and reviewed in 8 ). In this review, we use the term YAP/TAZ when it has been shown that YAP and TAZ share the mentioned regulations or functions.…”

Section: Canonical Hippo Pathway Componentsmentioning

confidence: 99%

The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases

Feltri

Weaver

Belin

et al. 2021

J Peripheral Nervous Sys

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Initially identified in Drosophila, the Hippo signaling pathway regulates how cells respond to their environment by controlling proliferation, migration and differentiation. Many recent studies have focused on characterizing Hippo pathway function and regulation in mammalian cells. Here, we present a brief overview of the major components of the Hippo pathway, as well as their regulation and function. We comprehensively review the studies that have contributed to our understanding of the Hippo pathway in the function of the peripheral nervous system and in peripheral nerve diseases. Finally, we discuss innovative approaches that aim to modulate Hippo pathway components in diseases of the peripheral nervous system.

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YAP and TAZ Are Not Identical Twins

Cited by 101 publications

References 95 publications

The essential role of TAZ in normal tissue homeostasis

The essential role of TAZ in normal tissue homeostasis

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases

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