Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 601-610 |
| Number of pages | 10 |
| Journal | ACS Chemical Biology |
| Volume | 12 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 17 2017 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
Cite this
Structural Insights into the Regulation of Hippo Signaling. / Cairns, Leah; Tran, Thao; Kavran, Jennifer.
In: ACS Chemical Biology, Vol. 12, No. 3, 17.03.2017, p. 601-610.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Structural Insights into the Regulation of Hippo Signaling
AU - Cairns, Leah
AU - Tran, Thao
AU - Kavran, Jennifer
PY - 2017/3/17
Y1 - 2017/3/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85015764796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85015764796&partnerID=8YFLogxK
U2 - 10.1021/acschembio.6b01058
DO - 10.1021/acschembio.6b01058
M3 - Review article
C2 - 28150487
AN - SCOPUS:85015764796
VL - 12
SP - 601
EP - 610
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 3
ER -