Tubulin cofactor A gene silencing in mammalian cells induces changes in microtubule cytoskeleton, cell cycle arrest and cell death.
Microtubules are polymers of alpha/beta-tubulin participating in essential cell functions. A multistep process involving distinct molecular chaperones and cofactors produces new tubulin heterodimers competent to polymerise. In vitro cofactor A (TBCA) interacts with beta-tubulin in a quasi-native state behaving as a molecular chaperone. We have used siRNA to silence TBCA expression in HeLa and MCF-7 mammalian cell lines. TBCA is essential for cell viability and its knockdown produces a decrease in the amount of soluble tubulin, modifications in microtubules and G1 cell cycle arrest. In MCF-7 cells, cell death was preceded by a change in cell shape resembling differentiation.
Nolasco
Sofia
S
Instituto Gulbenkian de Ciência, Apartado 14, 2781-901 Oeiras, Portugal.
Bellido
Javier
J
Gonçalves
João
J
Zabala
Juan Carlos
JC
Soares
Helena
H
D008841:Actin Cytoskeleton / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; C503328:TBCA protein, human; D014404:Tubulin; C505520:CASP7 protein, human; D053179:Caspase 7; D020169:Caspases