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Chromosome alignment-maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl-1 expression.

ABSTRACT: Antimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus can be a way to overcome the drug resistance. Here we found that depletion of a mitotic regulator, CHAMP1 (chromosome alignment-maintaining phosphoprotein, CAMP), accelerates the timing of mitotic cell death after mitotic arrest. Live cell imaging revealed that CHAMP1-depleted cells died earlier than mock-treated cells in the presence of antimitotic drugs that resulted in the reduction of cells undergoing mitotic slippage. Depletion CHAMP1 reduces the expression of antiapoptotic Bcl-2 family proteins, especially Mcl-1. We found that CHAMP1 maintains Mcl-1 expression both at protein and mRNA levels independently of the cell cycle. At the protein level, CHAMP1 maintains Mcl-1 stability by suppressing proteasome-dependent degradation. Depletion of CHAMP1 reduces cell viability, and exhibits synergistic effects with antimitotic drugs. Our data suggest that CHAMP1 plays a role in the maintenance of Mcl-1 expression, implying that CHAMP1 can be a target to overcome the resistance to antimitotic drugs.

SUBMITTER: Hino M

PROVIDER: S-EPMC8409433 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Chromosome alignment-maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl-1 expression.

Hino Maho M Iemura Kenji K Ikeda Masanori M Itoh Go G Tanaka Kozo K

Cancer science 20210716 9

Antimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus can be a way to overcome the drug resistance. Here we found that depletion of a mitotic regulator, CHAMP1 (chromosome alignment-maintaining phosphoprotein, CAMP), accelerates the timing of mitotic cell ...[more]

PMID: 34107118

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Dataset Information

Chromosome alignment-maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl-1 expression.

Publications

Chromosome alignment-maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl-1 expression.

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