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| Status |
Public on Dec 01, 2019 |
| Title |
STRIPAK directs PP2A activity to promote oncogenic transformation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
We evaluated the effects of suppressing MAP4K4 on transcriptome and YAP1 pathway based on the observation that partial suppression of MAP4K4 leads to transformation through activation of YAP1.
Mutations and deletions involving subunits of the serine-threonine phosphatase PP2A occur in a broad range of human cancers, and partial loss of PP2A function contributes to cell transformation. In particular, displacement of regulatory B subunits by the viral oncoprotein SV40 small-t antigen (ST) or mutation or deletion of PP2A subunits alters the abundance and types of PP2A complexes in cells and induces cell transformation in human cells. Here we show that ST not only displaces common PP2A B subunits but also promotes PP2A A-C subunit interactions with a set of alternative B subunits (B’’’, striatins) that are components of the Striatin-interacting phosphatase and kinase (STRIPAK) complex. We found that members of the STRIPAK complex are required for ST-PP2A induced cell transformation. PP2A interacts with and dephosphorylates the STRIPAK-associated kinase MAP4K4, which induces cell transformation in part through the regulation of the Hippo pathway effector YAP1. These observations identify an unanticipated role of MAP4K4 in transformation and show that the STRIPAK complex plays a key role in defining PP2A specificity and activity.
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| Overall design |
Stable cell line expressing shRNA targeting MAP4K4 or Luciferase control HEK cells immortalized with hTERT, SV40 Large-T antigen, and H-RAS(G12V) was used to perform transcriptome analysis.
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| Contributor(s) |
Kim JW, Kim M, DeCaprio J, Hahn W |
| Citation(s) |
31913126 |
| |
| Submission date |
Aug 07, 2018 |
| Last update date |
Feb 03, 2020 |
| Contact name |
Jong Wook Kim |
| E-mail(s) |
jongw@broadinstitute.org
|
| Organization name |
Broad Institute
|
| Department |
Cancer Program
|
| Street address |
45 Main Street
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA485011 |
| SRA |
SRP156614 |
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