Authors

R Mu, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
Y-B Wang, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
M Wu, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
Y Yang, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
W Song, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
T Li, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
W-N Zhang, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
B Tan, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
A-L Li, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
N Wang, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
Q Xia, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
W-L Gong, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
Chenguang Wang, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
T Zhou, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
N Guo, Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China
Z-H Sang, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing
H-Y Li, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing

Document Type

Article

Publication Date

3-2014

Comments

This article is the final published version in Cell Death and Disease
Volume 5, Issue 3, March 2014, Article number e1151.


The published version is available at DOI: 10.1038/cddis.2014.117. Copyright © Nature Publishing Group

Abstract

Disturbing mitotic progression via targeted anti-mitotic therapy is an attractive strategy for cancer treatment. Therefore, the exploration and elucidation of molecular targets and pathways in mitosis are critical for the development of anti-mitotic drugs. Here, we show that cell division cycle 5-like (Cdc5L), a pre-mRNA splicing factor, is a regulator of mitotic progression. Depletion of Cdc5L causes dramatic mitotic arrest, chromosome misalignments and sustained activation of spindle assembly checkpoint, eventually leading to mitotic catastrophe. Moreover, these defects result from severe impairment of kinetochore-microtubule attachment and serious DNA damage. Genome-wide gene expression analysis reveals that Cdc5L modulates the expression of a set of genes involved in the mitosis and the DNA damage response. We further found that the pre-mRNA splicing efficiency of these genes were impaired when Cdc5L was knocked down. Interestingly, Cdc5L is highly expressed in cervical tumors and osteosarcoma. Finally, we demonstrate that downregulation of Cdc5L decreases the cell viability of related tumor cells. These results suggest that Cdc5L is a key regulator of mitotic progression and highlight the potential of Cdc5L as a target for cancer therapy.

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