Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus

Faculty Science Year: 2018
Type of Publication: ZU Hosted Pages:
Authors:
Journal: Open Biology Royal Society_Open Biology 8(6):170272Royal Society Volume:
Keywords : Constitutive regulation , mitochondrial morphology , Aurora , kinase    
Abstract:
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.
   
     
 
       

Author Related Publications

  • Ahmed Mohamed Abdelbaky Abedulaal, "AURKA destruction is decoupled from its activity at mitotic exit but essential to suppress interphase activity", The Company of Biologists, 2020 More
  • Ahmed Mohamed Abdelbaky Abedulaal, "Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool", Nature, 2021 More
  • Ahmed Mohamed Abdelbaky Abedulaal, "Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool", Nature, 2021 More
  • Ahmed Mohamed Abdelbaky Abedulaal, "Revisiting degron motifs in human AURKA required for its targeting by APC/C-FZR1", EMBO Press, Rockefeller University Press and Cold Spring Harbor Laboratory Press, 2022 More

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