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Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras.

Abstract:

K-Ras mutations are frequent in colorectal cancer (CRC), albeit K-Ras is the only Ras isoform that can elicit apoptosis. Here, we show that mutant K-Ras directly binds to the tumor suppressor RASSF1A to activate the apoptotic MST2-LATS1 pathway. In this pathway LATS1 binds to and sequesters the ubiquitin ligase Mdm2 causing stabilization of the tumor suppressor p53 and apoptosis. However, mutant Ras also stimulates autocrine activation of the EGF receptor (EGFR) which counteracts mutant K-Ras...

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Publication status:
Published

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Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Role:
Author
Journal:
Molecular cell More from this journal
Volume:
44
Issue:
6
Pages:
893-906
Publication date:
2011-12-01
DOI:
EISSN:
1097-4164
ISSN:
1097-2765
Language:
English
Keywords:
Pubs id:
pubs:222331
UUID:
uuid:6aa75e18-2722-49d2-bb1d-9885435c5842
Local pid:
pubs:222331
Source identifiers:
222331
Deposit date:
2012-12-19

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