BCAT1 redox function maintains mitotic fidelity

Journal article


Francois, L., Boskovic, P., Knerr, J., He, W., Sigismondo, G., Schwan, C., More, T. H., Schlotter, M., Conway, M., Krijgsveld, J., Hiller, K. and Grosse, R. 2023. BCAT1 redox function maintains mitotic fidelity. Cell Reports. 42 (3), pp. 1-25.
AuthorsFrancois, L., Boskovic, P., Knerr, J., He, W., Sigismondo, G., Schwan, C., More, T. H., Schlotter, M., Conway, M., Krijgsveld, J., Hiller, K. and Grosse, R.
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.

KeywordsBCAT1; CP: Cell biology; cancer; chromosome segregation; metabolism; mitosis; moonlighting function; redox; stem cells
Year2023
JournalCell Reports
Journal citation42 (3), pp. 1-25
PublisherElsevier
Web address (URL)https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01379-1
Accepted author manuscript
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File Access Level
Open
Output statusPublished
Publication dates
Online18 Oct 2022
Publication process dates
Deposited14 Jul 2023
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License: CC BY-NC-ND 4.0
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