PDGFR-alpha and STMN1 cooperate to exacerbate cytotoxic effects of vinblastine (WP4398)

Mus musculus

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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.

Authors

Kristina Hanspers , Egon Willighagen , and Eric Weitz

Activity

last edited

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Organisms

Mus musculus

Communities

ExRNA

Annotations

Disease Ontology

glioblastoma

Pathway Ontology

cell cycle pathway

Participants

Label Type Compact URI Comment
Vinblastine Metabolite chebi:27375
Pdgfra GeneProduct ensembl:ENSMUSG00000029231
Stmn1 GeneProduct ensembl:ENSMUSG00000028832

References

  1. A PDGFRα-driven mouse model of glioblastoma reveals a stathmin1-mediated mechanism of sensitivity to vinblastine. Jun HJ, Appleman VA, Wu HJ, Rose CM, Pineda JJ, Yeo AT, et al. Nat Commun. 2018 Aug 6;9(1):3116. PubMed Europe PMC Scholia