RGD Reference Report - Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint. - Rat Genome Database

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Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint.

Authors: Eves, EM  Shapiro, P  Naik, K  Klein, UR  Trakul, N  Rosner, MR 
Citation: Eves EM, etal., Mol Cell. 2006 Aug;23(4):561-74.
RGD ID: 2302821
Pubmed: PMID:16916643   (View Abstract at PubMed)
PMCID: PMC1626587   (View Article at PubMed Central)
DOI: DOI:10.1016/j.molcel.2006.07.015   (Journal Full-text)

Raf kinase inhibitory protein (RKIP or PEBP) is an inhibitor of the Raf/MEK/MAP kinase signaling cascade and a suppressor of cancer metastasis. We now show that RKIP associates with centrosomes and kinetochores and regulates the spindle checkpoint in mammalian cells. RKIP depletion causes decreases in the mitotic index, the number of metaphase cells, and traversal times from nuclear envelope breakdown to anaphase, and an override of mitotic checkpoints induced by spindle poisons. Raf-1 depletion or MEK inhibition reverses the reduction in the mitotic index, whereas hyperactivation of Raf mimics the RKIP-depletion phenotype. Finally, RKIP depletion or Raf hyperactivation reduces kinetochore localization and kinase activity of Aurora B, a regulator of the spindle checkpoint. These results indicate that RKIP regulates Aurora B kinase and the spindle checkpoint via the Raf-1/MEK/ERK cascade and demonstrate that small changes in the MAP kinase (MAPK) pathway can profoundly impact the fidelity of the cell cycle.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Pebp1Ratpositive regulation of mitotic nuclear division  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pebp1  (phosphatidylethanolamine binding protein 1)


Additional Information