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AJUBA LIM Proteins Limit Hippo Activity in Proliferating Cells by Sequestering the Hippo Core Kinase Complex in the Cytosol
- Source :
- Molecular and Cellular Biology
- Publication Year :
- 2016
-
Abstract
- The Hippo pathway controls organ growth and is implicated in cancer development. Whether and how Hippo pathway activity is limited to sustain or initiate cell growth when needed is not understood. The members of the AJUBA family of LIM proteins are negative regulators of the Hippo pathway. In mammalian epithelial cells, we found that AJUBA LIM proteins limit Hippo regulation of YAP, in proliferating cells only, by sequestering a cytosolic Hippo kinase complex in which LATS kinase is inhibited. At the plasma membranes of growth-arrested cells, AJUBA LIM proteins do not inhibit or associate with the Hippo kinase complex. The ability of AJUBA LIM proteins to inhibit YAP regulation by Hippo and to associate with the kinase complex directly correlate with their capacity to limit Hippo signaling during Drosophila wing development. AJUBA LIM proteins did not influence YAP activity in response to cell-extrinsic or cell-intrinsic mechanical signals. Thus, AJUBA LIM proteins limit Hippo pathway activity in contexts where cell proliferation is needed.
- Subjects :
- 0301 basic medicine
endocrine system
animal structures
Biology
Protein Serine-Threonine Kinases
03 medical and health sciences
Cytosol
Animals
Drosophila Proteins
Humans
Wings, Animal
Hippo Signaling Pathway
Spotlight
Molecular Biology
Adaptor Proteins, Signal Transducing
Cell Proliferation
Hippo signaling pathway
Cell growth
Kinase
fungi
Intracellular Signaling Peptides and Proteins
Epithelial Cells
YAP-Signaling Proteins
Cell Biology
Articles
LIM Domain Proteins
Phosphoproteins
Cell biology
body regions
030104 developmental biology
Drosophila melanogaster
HEK293 Cells
Hippo signaling
MCF-7 Cells
Cancer development
sense organs
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 36
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular biology
- Accession number :
- edsair.doi.dedup.....aaaa87724deb50a5447646d5205ea90f