Structural Insights into the Regulation of Hippo Signaling.
During development, the Hippo pathway regulates the balance between cell proliferation and apoptosis to control organ size. Appropriate Hippo signaling is associated with stem cell maintenance, while inappropriate signaling can result in tumorigenesis and cancer. Cellular and genetic investigations have identified core components and determined that complex formation and protein phosphorylation are crucial regulatory events. The recent spate of high-resolution structures of Hippo pathway components have begun to reveal the molecular mechanisms controlling these events, including the molecular determinates of complex formation between YAP and TEAD, the role of phosphorylation in controlling complex formation by Mob, and the conformational changes accompanying Mst1/2 kinase domain activation. We will review these advances and revisit previous structures to provide a comprehensive overview of the structural changes associated with the regulation of this pathway as well as discuss areas that could benefit from further mechanistic studies.
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health and ‡Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University , Baltimore, Maryland 21205, United States.
Leah
L
Cairns
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health and ‡Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University , Baltimore, Maryland 21205, United States.
Thao
T
Tran
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health and ‡Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University , Baltimore, Maryland 21205, United States.
Jennifer M
0000-0001-9117-5209
JM
Kavran
D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D000099317:Hippo Kinases
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases