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Uncovering new substrates for Aurora A kinase.

ABSTRACT: Aurora A is a serine/threonine kinase that is essential for a wide variety of cell-cycle-related events, but only a small number of its substrates are known. We present and validate a strategy by which to identify Aurora A substrates and their phosphorylation sites. We developed a computational approach integrating various types of biological information to generate a list of 90 potential Aurora substrates, with a prediction accuracy of about 80%. We also demonstrated the specific phosphorylation of NUSAP (nucleolar and spindle-associated protein) by Aurora A in vivo. Our results provide a means by which to develop an understanding of Aurora A function and suggest unexpected roles for this kinase.

SUBMITTER: Sardon T

PROVIDER: S-EPMC2999863 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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Uncovering new substrates for Aurora A kinase.

Sardon Teresa T Pache Roland A RA Stein Amelie A Molina Henrik H Vernos Isabelle I Aloy Patrick P

EMBO reports 20101112 12

Aurora A is a serine/threonine kinase that is essential for a wide variety of cell-cycle-related events, but only a small number of its substrates are known. We present and validate a strategy by which to identify Aurora A substrates and their phosphorylation sites. We developed a computational approach integrating various types of biological information to generate a list of 90 potential Aurora substrates, with a prediction accuracy of about 80%. We also demonstrated the specific phosphorylatio ...[more]

PMID: 21072059

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Aurora kinase inhibition triggers senescence in human melanoma cells

Project description:Phenotypically, there is a heterogeneous response of cancer cells to chemotherapy or targeted therapy. While therapeutically much attention is focused on cell death, there is growing evidence suggesting that a subpopulation of cancer cells undergo therapy-induced senescence. Depending on the therapy, dose and timing, senescence may be a dominant phenotype over cell death. An integrated FACS approach identified two types of therapy-induced senescence in human melanoma cells, irreversible senescence induced by Aurora kinase inhibition vs. transient senescence induced by B-RAF kinase inhibition. Autophagy and ER stress response precede and are required for therapy-induced senescence in cancer cells, mirroring their functions in normal cells undergoing oncogene-induced senescence. Importantly, autophagy serves a survival pathway for senescent cancer cells. Antagonizing autophagy converts therapy-induced senescence into cell death but paradoxically promotes cell proliferation or quiescence. Our work calls for a rationale-based design of combination therapy for cancer treatment that should lead to a greater synergy. There are three or four replicates per treatment per time point.

2015-06-05 | E-GEOD-38466 | biostudies-arrayexpress

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