BCAT1 redox function maintains mitotic fidelity

Cell Rep. 2022 Oct 18;41(3):111524. doi: 10.1016/j.celrep.2022.111524.

Abstract

The metabolic enzyme branched-chain amino acid transaminase 1 (BCAT1) drives cell proliferation in aggressive cancers such as glioblastoma. Here, we show that BCAT1 localizes to mitotic structures and has a non-metabolic function as a mitotic regulator. Furthermore, BCAT1 is required for chromosome segregation in cancer and induced pluripotent stem cells and tumor growth in human cerebral organoid and mouse syngraft models. Applying gene knockout and rescue strategies, we show that the BCAT1 CXXC redox motif is crucial for controlling cysteine sulfenylation specifically in mitotic cells, promoting Aurora kinase B localization to centromeres, and securing accurate chromosome segregation. These findings offer an explanation for the well-established role of BCAT1 in promoting cancer cell proliferation. In summary, our data establish BCAT1 as a component of the mitotic apparatus that safeguards mitotic fidelity through a moonlighting redox functionality.

Keywords: BCAT1; CP: Cell biology; cancer; chromosome segregation; metabolism; mitosis; moonlighting function; redox; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Branched-Chain*
  • Animals
  • Aurora Kinase B
  • Cysteine*
  • Disease Models, Animal
  • Humans
  • Mice
  • Oxidation-Reduction
  • Transaminases

Substances

  • Amino Acids, Branched-Chain
  • Aurora Kinase B
  • BCAT1 protein, human
  • Cysteine
  • Transaminases
  • Bcat1 protein, mouse