Investigating the role of the Anaphase-Promoting Complex/Cyclosome subunit APC5 during mitosis

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Tilotta, Maria Teresa (2019). Investigating the role of the Anaphase-Promoting Complex/Cyclosome subunit APC5 during mitosis. University of Birmingham. Ph.D.

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Abstract

The Anaphase-Promoting Complex/Cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that targets key cell cycle regulators for 26S proteasome-mediated degradation during mitosis and G1 phases of the cell cycle. APC/C activity is regulated through protein-protein interactions and post-translational modifications (PTMs). The precise role of individual APC/C subunits and their PTMs in the control of APC/C activity is not fully understood. Here we show that APC5 knockdown by RNA interference promotes either mitotic arrest or a delay in the ability of cells to progress through mitosis; a small but significant proportion of cells that progress through mitosis also display defects in cytokinesis. We also show that almost the entire cellular pool of the APC/C subunit, APC5 is phosphorylated during mitosis at S195 and that this phosphorylation event might play a crucial role in the control of APC/C during mitosis. We determined that the phosphorylated APC5 S195 species localized at centrosomes from prophase to anaphase whereupon it re-localized to midbodies during the late stages of mitosis and co-localized with known APC/C substrates. As such, our findings provide new insights into how phosphorylation regulates APC5 and the APC/C during mitosis and defines potential new roles for the APC/C in cytokinesis.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):