Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 29, Pages 11978-11983Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0900608106
Keywords
apoptosis; mitochondria; RNAi screen; signal transduction; GLK
Categories
Funding
- Medical Research Council [MC_U132674518] Funding Source: Medline
- MRC [MC_U132674518] Funding Source: UKRI
- Medical Research Council [MC_U132674518] Funding Source: researchfish
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Intracellular signal transduction networks involving protein kinases are important modulators of cell survival and cell death in multicellular organisms. Functional compromise of these networks has been linked to aberrant apoptosis in diseases such as cancer. To identify novel kinase regulators of cell death, we conducted an RNAi-based screen to identify modulators of the intrinsic apoptosis pathway. Using this approach, we identified MAP4K3 as a novel apoptosis inducer. Here, we present evidence that this pro-apoptotic kinase orchestrates activation of BAX via the concerted posttranscriptional modulation of PUMA, BAD, and BIM. Additionally, we found decreased levels of this kinase in pancreatic cancer samples, suggesting a tumor suppressor role for MAP4K3 in pancreatic tumorigenesis.
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