Expression of TDRD9 in a subset of lung carcinomas by CpG island hypomethylation protects from DNA damage

Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochond...

Descripción completa

Detalles Bibliográficos
Autores: Grant, Rhys, Abdelfattah, Ahmed, Bertoldi, Alessia, Gavilán, María P., Mansfeld, Jörg, Glover, David M., Lindon, Catherine
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/180542
Acceso en línea:http://hdl.handle.net/10261/180542
Access Level:acceso abierto
Palabra clave:AURKA
Mitochondria
Mitochondrial dynamics
Descripción
Sumario:Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE-1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, because an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.