PDGFR-alpha and STMN1 cooperate to exacerbate cytotoxic effects of vinblastine (Mus musculus)

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1PolymerizationSpindle assembly checkpoint(SAC)VinblastinePdgfraStmn1Mitotic slippageApoptosisDepolymerizationStmn1PP


Description

Stathmin (SMTMN1) normally binds to alpha-beta tubulin heterodimers, but this process is negatively regulated by phosphorylation. In this way phosphorylated Stathmin indirectly promotes polymerization. PDGFRα dephosphorylates STMN1, which leads to increased tubulin depolymerization. Vinblastine inhibits polymerization, effectively resulting in depolymerization. During mitosis, this triggers the defense mechanism "spindle assembly checkpoint" (SAC), which and results in either apoptosis or mitotic slippage.

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Bibliography

  1. Jun HJ, Appleman VA, Wu HJ, Rose CM, Pineda JJ, Yeo AT, Delcuze B, Lee C, Gyuris A, Zhu H, Woolfenden S, Bronisz A, Nakano I, Chiocca EA, Bronson RT, Ligon KL, Sarkaria JN, Gygi SP, Michor F, Mitchison TJ, Charest A; ''A PDGFRα-driven mouse model of glioblastoma reveals a stathmin1-mediated mechanism of sensitivity to vinblastine.''; Nat Commun, 2018 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
117929view10:40, 23 May 2021EweitzModified title
98995view12:02, 20 October 2018EgonwReplaced a secondary ChEBI identifier.
98993view23:23, 19 October 2018KhanspersOntology Term : 'cell cycle pathway' added !
98992view23:22, 19 October 2018KhanspersOntology Term : 'glioblastoma multiforme' added !
98991view23:20, 19 October 2018KhanspersModified description
98990view23:20, 19 October 2018KhanspersModified description
98989view23:09, 19 October 2018KhanspersNew pathway

External references

DataNodes

NameTypeDatabase referenceComment
PdgfraGeneProductENSMUSG00000029231 (Ensembl)
Stmn1GeneProductENSMUSG00000028832 (Ensembl)
VinblastineMetaboliteCHEBI:9983 (ChEBI)

Annotated Interactions

No annotated interactions

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