The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell

Autor: Shenghong Ma, Kun-Liang Guan, Kimberly C. Lin, Bing Ren, Zhen Ye, Jerrell L. Moore rd, Yunjiang Qiu, Frederick E. Tan, Steven W. Plouffe
Rok vydání: 2018
Předmět:
TAZ
0301 basic medicine
Hippo pathway
Cell
WWTR1
Yes-associated protein
Medical and Health Sciences
Biochemistry
cell biology
Homeostasis
2.1 Biological and endogenous factors
Aetiology
Tissue homeostasis
Effector
Adaptor Proteins
Biological Sciences
Cell biology
medicine.anatomical_structure
Hippo signaling
Signal Transduction
Biotechnology
Cell physiology
Biochemistry & Molecular Biology
1.1 Normal biological development and functioning
Protein Serine-Threonine Kinases
Biology
Cell Physiological Phenomena
gene knockout
03 medical and health sciences
CRISPR/Cas
Underpinning research
Genetics
medicine
Humans
Hippo Signaling Pathway
Molecular Biology
Gene knockout
Adaptor Proteins
Signal Transducing
Hippo signaling pathway
Tumor Suppressor Proteins
Gene Expression Profiling
Signal Transducing
YAP-Signaling Proteins
Cell Biology
Phosphoproteins
HEK293 Cells
030104 developmental biology
Chemical Sciences
CRISPR-Cas Systems
Acyltransferases
Transcription Factors
Zdroj: The Journal of biological chemistry, vol 293, iss 28
ISSN: 0021-9258
DOI: 10.1074/jbc.ra118.002715
Popis: The Hippo pathway plays an important role in regulating tissue homeostasis, and its effectors, the transcriptional co-activators Yes-associated protein (YAP) and WW domain-containing transcription regulator 1 (WWTR1 or TAZ), are responsible for mediating the vast majority of its physiological functions. Although YAP and TAZ are thought to be largely redundant and similarly regulated by Hippo signaling, they have developmental, structural, and physiological differences that suggest they may differ in their regulation and downstream functions. To better understand the functions of YAP and TAZ in the Hippo pathway, using CRISPR/Cas9, we generated YAP KO, TAZ KO, and YAP/TAZ KO cell lines in HEK293A cells. We evaluated them in response to many environmental conditions and stimuli and used RNA-Seq to compare their transcriptional profiles. We found that YAP inactivation has a greater effect on cellular physiology (namely, cell spreading, volume, granularity, glucose uptake, proliferation, and migration) than TAZ inactivation. However, functional redundancy between YAP and TAZ was also observed. In summary, our findings confirm that the Hippo pathway effectors YAP and TAZ are master regulators for multiple cellular processes but also reveal that YAP has a stronger influence than TAZ.
Databáze: OpenAIRE
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