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Targeting Mnks for cancer therapy
- Source :
- Oncotarget, Scopus-Elsevier
- Publication Year :
- 2012
-
Abstract
- Deregulation of protein synthesis is a common event in human cancer and a key player in translational control is eIF4E. Elevated expression levels of eIF4E promote cancer development and progression. Recent findings suggest that eIF4E activity is a key determinant of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK mediated tumorigenic activity and targeting eIF4E should have a major impact on these pathways in human cancer. The function of eIF4E is modulated through phosphorylation of a conserved serine (Ser209) by Mnk1 and Mnk2 downstream of ERK. While the phosphorylation event is necessary for oncogenic transformation, it seems to be dispensable for normal development. Hence, pharmacologic Mnk inhibitors may provide non-toxic and effective anti-cancer strategy. Strong circumstantial evidence indicates that Mnk inhibition presents attractive therapeutic potential, but the lack of selective Mnk inhibitors has so far confounded pharmacological target validation and clinical development. Refereed/Peer-reviewed
- Subjects :
- MAPK/ERK pathway
Proto-Oncogene Proteins c-akt
Mnk
Reviews
Biology
Protein Serine-Threonine Kinases
targeted cancer therapy
PI3K
Mnk Inhibitors
Protein Structure, Secondary
Serine
Mice
Phosphatidylinositol 3-Kinases
Animals
Humans
Targeted Cancer Therapy
Amino Acid Sequence
Phosphorylation
Protein kinase B
PI3K/AKT/mTOR pathway
mnk
mnk inhibitors
TOR Serine-Threonine Kinases
Akt
EIF4E
Intracellular Signaling Peptides and Proteins
Raf
Pi3K
MAPK
Cell biology
Eukaryotic Initiation Factor-4E
Oncology
structure based drug design
eIF4E
ras Proteins
mTOR
Structure based drug design
raf Kinases
Mitogen-Activated Protein Kinases
Sequence Alignment
Ras
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 3
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....5eda6a090c7a2496ed665404fbdbb3b3