Aurora B-dependent phosphorylation of Ataxin-10 promotes the interaction between Ataxin-10 and Plk1 in cytokinesis

Abstract

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCT expansion in the ATXN10 gene. Previous investigations have identified that depletion of Ataxin-10, the gene product, leads to cellular apoptosis and cytokinesis failure. Herein we identify the mitotic kinase Aurora B as an Ataxin-10 interacting partner. Aurora B interacts with and phosphorylates Ataxin-10 at S12, as evidenced by in vitro kinase and mass spectrometry analysis. Both endogenous and S12-phosphorylated Ataxin-10 localizes to the midbody during cytokinesis, and cytokinetic defects induced by inhibition of ATXN10 expression is not rescued by the S12A mutant. Inhibition of Aurora B or expression of the S12A mutant renders reduced interaction between Ataxin-10 and polo-like kinase 1 (Plk1), a kinase previously identified to regulate Ataxin-10 in cytokinesis. Taken together, we propose a model that Aurora B phosphorylates Ataxin-10 at S12 to promote the interaction between Ataxin-10 and Plk1 in cytokinesis. These findings identify an Aurora B-dependent mechanism that implicates Ataxin-10 in cytokinesis.

Checkpoint kinase 1–induced phosphorylation of O-linked β-N-acetylglucosamine transferase regulates the intermediate filament network during cytokinesis

“…Protocols to synchronize cells in the cytokinetic phase were described before (31). Briefly, cell cultures were first blocked by double thymidine, and collected 9 h after releasing from the second thymidine block.…”

“…IP and IB experiments were performed as described before (31). The following primary antibodies were used for IB: RL2 (1:500), anti-OGT (1:1000), anti-Chk1(1:1000), anti-␤-actin (1:10000), anti-OGT-pSer-20 (1:1000), anti-vimentin (1:1000), anti-vimentin-pSer-71(1:1000), anti-Myc (1:5000), anti-HA (1:5000), and anti-FLAG M2 (1:5000) (Sigma).…”

Phosphorylation of LSD1 by PLK1 promotes its chromatin release during mitosis

“…Phosphorylation site mapping by mass spectrometry was performed as described previously [23]. Briefly, in vitro phosphorylated proteins were precipitated with TCA and resuspended in a buffer containing 8 M urea, 100 mM Tris, pH8.5.…”

c‐Abl tyrosine kinase regulates neutrophil crawling behavior under fluid shear stress via Rac/PAK/LIMK/cofilin signaling axis

“…The extracted peptides containing phosphorylation sites of Vav1 from gel were identified by LC-MS/MS as previously described. 24…”