Recent Progress on the Localization of PLK1 to the Kinetochore and Its Role in Mitosis

Abstract

The accurate distribution of the replicated genome during cell division is essential for cell survival and healthy organismal development. Errors in this process have catastrophic consequences, such as birth defects and aneuploidy, a hallmark of cancer cells. PLK1 is one of the master kinases in mitosis and has multiple functions, including mitotic entry, chromosome segregation, spindle assembly checkpoint, and cytokinesis. To dissect the role of PLK1 in mitosis, it is important to understand how PLK1 localizes in the specific region in cells. PLK1 localizes at the kinetochore and is essential in spindle assembly checkpoint and chromosome segregation. However, how PLK1 localizes at the kinetochore remains elusive. Here, we review the recent literature on the kinetochore recruitment mechanisms of PLK1 and its roles in spindle assembly checkpoint and attachment between kinetochores and spindle microtubules. Together, this review provides an overview of how the local distribution of PLK1 could regulate major pathways in mitosis.

DNA damage checkpoint execution and the rules of its disengagement

“…Suppression of PLK1 does not affect mitotic entry during normal cell cycle but it significantly delays recovery from checkpoint arrest ( van Vugt et al, 2004 ). This delay can be alleviated by depletion of WEE1 suggesting that WEE1 may be the downstream target of PLK1 during checkpoint recovery ( van Vugt and Medema, 2005 ; Kim, 2022 ). PLK1 also mediates degradation of Claspin leading to disabling of CHK1 ( Mailand et al, 2006 ; Mamely et al, 2006 ).…”

KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2

“…Accurate separation of replicative genomes to daughter cells during cell division is crucial for cell survival and development. The kinetochore, a large multiprotein complex, is a key component of this process and guides the progression of the cell cycle 6 . Dysregulation of kinetochore/centromere proteins mediates abnormal cell mitosis and influences proliferation signaling pathways of cancer cells 7 .…”

“…The kinetochore, a large multiprotein complex, is a key component of this process and guides the progression of the cell cycle. 6 Dysregulation of kinetochore/centromere proteins mediates abnormal cell mitosis and influences proliferation signaling pathways of cancer cells. 7 Kinetochore associated protein 1 (KNTC1) gene, located on human chromosome 12q24.31t, encodes a protein that is an evolutionarily conserved subunit of the kinetochore protein complex and plays a crucial role in spindle assembly and chromosome disjunction.…”