*2.3. TRIOBP-1 in the Cell Cycle*

TRIOBP-1 is essential for correct mitotic progression, with its knockdown in cells leading to multipolar spindle formation [14]. Similar effects are also observed when expression levels of TRIOBP-1 expression were increased, through knockdown of ubiquitin ligase HECTD3 [32]. This suggests

that regulation of TRIOBP-1 expression is of significant importance. The most likely mechanism by which TRIOBP-1 affects mitotic progression is through its interaction with TRF1 (Telomere Repeat Factor 1 [22,33]). TRF1 is found at the telomeres of cells, and is involved in both telomere stability and cell cycle regulation. Notably, the localization of TRF1 during mitosis is dependent on that of TRIOBP-1 [14]. The localization of TRIOBP-1 during the cell cycle is itself regulated by two kinases, with PLK1 in particular being required for both its localization in prophase and metaphase, and also for its interaction with TRF1 [14,21]. Strikingly, mutation of the threonine in TRIOBP-1 that is phosphorylated by PLK1 leads to mitotic arrest in prometaphase [21]. Specifically, the chromosomes fail to segregate, highlighting the importance of TRIOBP-1 in this process. While there is some evidence that actin plays a role in mitosis, it remains to be determined whether the function of TRIOBP-1 in mitosis is directly related to its F-actin stabilization effect.
