Hippo signaling is intrinsically regulated during cell cycle progression by APC/C.

Authors:
Wantae Kim
Wantae Kim
The University of Seoul
Yong Suk Cho
Yong Suk Cho
Hangang Sacred Heart Hospital
Xiaohui Wang
Xiaohui Wang
Modern Research Center for Traditional Chinese Medicine
United States
Ogyi Park
Ogyi Park
National Institutes of Health
United States
Xueyan Ma
Xueyan Ma
Institute of Pharmacy
Germany
Hanjun Kim
Hanjun Kim
The University of Seoul
Wenjian Gan
Wenjian Gan
Harvard Medical School
United States
Eek-Hoon Jho
Eek-Hoon Jho
University of Seoul
South Korea

Proc Natl Acad Sci U S A 2019 May 18;116(19):9423-9432. Epub 2019 Apr 18.

Department of Developmental Biology, Harvard Stem Cell Institute, Harvard School of Dental Medicine, Boston, MA 02215;

The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/C represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1821370116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511010PMC
May 2019
8 Reads

Article Mentions


Provided by Crossref Event Data
twitter
Twitter:
May 1, 2019, 4:18 am EST

Publication Analysis

Top Keywords

hippo signaling
20
cell cycle
16
lats kinases
8
signaling regulation
8
eye wing
8
cycle progression
8
signaling
5
lats
5
hippo
5
kinases promote
4
recognizes lats
4
cdh1 recognizes
4
signaling activities
4
activities cdh1
4
control result
4
degradation yap/taz
4
regulation lats
4
phosphorylation cell
4
cycle control
4
yap/taz regulation
4

References

(Supplied by CrossRef)

Similar Publications