The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that ensures the fidelity of chromosomes segregation. Reduced expression of some of its components weakens the SAC and induces chromosome instability and aneuploidy, which are both well-known hallmarks of cancer cells. Centromere protein-E (CENP-E) is a crucial component of the SAC and its function is to facilitate kinetochore microtubule attachment required to achieve and maintain chromosome alignment. The present study investigates the possible role of p14ARFas a controller of aneuploid cells proliferation. We used RNA interference to induce aneuploidy by partial depletion of CENP-E in human primary fibroblasts (IMR90) and in near diploid tumor cells (HCT116). In contrast to IMR90 aneuploid cell number, which was drastically reduced and leaned towards the WT condition, HCT116 aneuploid cell numbers were slightly decreased at later time points. This euploidy restoration was accompanied by increased p14ARFexpression in IMR90 cells and followed ectopic p14ARFre-expression in p14ARF-null HCT116 cells. Collectively, our results suggest that hampering proliferation of aneuploid cells could be an additional role of the p14ARFtumor suppressor.

Veneziano L, B.V. (2019). Proliferation of aneuploid cells induced by CENP-E depletion is counteracted by the p14ARFtumor suppressor. MOLECULAR GENETICS AND GENOMICS, 294(1), 149-158 [10.1007/s00438-018-1495-5].

Proliferation of aneuploid cells induced by CENP-E depletion is counteracted by the p14ARFtumor suppressor

Veneziano L;Barra V;Cilluffo D
Membro del Collaboration Group
;
Di Leonardo A.
Writing – Original Draft Preparation
2019-01-01

Abstract

The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that ensures the fidelity of chromosomes segregation. Reduced expression of some of its components weakens the SAC and induces chromosome instability and aneuploidy, which are both well-known hallmarks of cancer cells. Centromere protein-E (CENP-E) is a crucial component of the SAC and its function is to facilitate kinetochore microtubule attachment required to achieve and maintain chromosome alignment. The present study investigates the possible role of p14ARFas a controller of aneuploid cells proliferation. We used RNA interference to induce aneuploidy by partial depletion of CENP-E in human primary fibroblasts (IMR90) and in near diploid tumor cells (HCT116). In contrast to IMR90 aneuploid cell number, which was drastically reduced and leaned towards the WT condition, HCT116 aneuploid cell numbers were slightly decreased at later time points. This euploidy restoration was accompanied by increased p14ARFexpression in IMR90 cells and followed ectopic p14ARFre-expression in p14ARF-null HCT116 cells. Collectively, our results suggest that hampering proliferation of aneuploid cells could be an additional role of the p14ARFtumor suppressor.
2019
Settore BIO/18 - Genetica
Veneziano L, B.V. (2019). Proliferation of aneuploid cells induced by CENP-E depletion is counteracted by the p14ARFtumor suppressor. MOLECULAR GENETICS AND GENOMICS, 294(1), 149-158 [10.1007/s00438-018-1495-5].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/301685
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