Abstract
Cytokinesis is the last step of cell division and is concluded by the abscission of the intercellular bridge that connects two daughter cells. The tight regulation of cytokinesis completion is essential because cytokinesis failure is associated with various human diseases. Here, we report that iASPP, a member of the apoptosis-stimulating proteins of p53 (ASPP) family, is required for proper cell division. iASPP depletion results in abnormal midbody structure and failed cytokinesis. We used protein affinity purification methods to identify the functional partners of iASPP. We found that iASPP associates with centrosomal protein of 55 kDa (CEP55), an important cytokinetic abscission regulator. Mechanically, iASPP acts as a PP1-targeting subunit to facilitate the interaction between PP1 and CEP55 and to remove PLK1-mediated Ser436 phosphorylation in CEP55 during late mitosis. The latter step is critical for the timely recruitment of CEP55 to the midbody. The present observations revealed a previously unrecognized function of iASPP in cytokinesis. This function, in turn, likely contributes to the roles of iASPP in tumor development and genetic diseases.
Highlights
Cytokinesis is the final stage of cell division, and its completion results in the irreversible partitioning of a single eukaryotic cell into two daughter cells
We first examined the interaction between iASPP and Centrosomal protein of 55 kDa (CEP55) by coexpressing FLAG–HA(FH)–iASPP and MycCEP55 in 293T cells. 293T cells were used for exogenous transfection since high efficiency transfection can be achieved in 293T cells
We isolated the FH-CEP55 complex from HeLa cells through tandem affinity purification (TAP) methods and determined the proteins present in the complex, we found ALIX, TSG101 and other ESCRT-I subunits, were abundantly present in FH-CEP55 complex, we did not identify any peptides corresponding to iASPP
Summary
Cytokinesis is the final stage of cell division, and its completion results in the irreversible partitioning of a single eukaryotic cell into two daughter cells. Similar to the other stages of cell division, cytokinesis is necessary for the proper growth and development of many organisms[2]. The final stage of cytokinesis, termed abscission, requires the breakage of the midbody, a thin membranous stalk that connects nascent daughter cells. Cytokinetic abscission is a complex process that requires tight spatiotemporal regulation to ensure the equal distribution of genomic and cytoplasmic material between two nascent daughter cells[3]. Centrosomal protein of 55 kDa (CEP55) localizes in the midbody and plays crucial roles in cytokinesis[5,6]. CEP55 acts as an adaptor that interacts with the central MKLP-1 component of the midbody and ESCRT-I subunits TSG101 and ALIX, which recruit the ESCRT-III
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