Kinesin-like protein KIF20A was first identified as a binding partner for the rab6 GTPase involved in protein transport at the Golgi apparatus []. It was later found to be a mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. It is phosphorylated by PLK1 at Ser-528 during mitosis, creating a docking site for PLK1 and recruiting PLK1 at central spindle. It contains a kinesin-motor domain and has a microtubule plus end-directed motility [].
The meiosis-specific kinetochore factor Meikin plays a crucial role in both mono-orientation and centromeric cohesion protection during meiosis I, partly by stabilizing the localization of the cohesin protector shugoshin, and also by recruiting Polo-like kinase PLK1 to the kinetochores. PLK1 is required for mono-orientation and the protection of centromeric cohesion [].
This entry represents the C-terminal domain of protein furry (Fry). Fry plays a crucial role in the structural integrity of mitotic centrosomes and in the maintenance of spindle bipolarity. This domain binds to polo-like kinase 1 (Plk1) through the polo-box domain (PBD) of Plk1 in a manner dependent on the cyclin-dependent kinase 1-mediated Fry phosphorylation, promoting Plk1 activity during early mitosis. Fry also binds to Aurora A and may function as a scaffold promoting the interaction between AURKA and PLK1, thereby enhancing AURKA-mediated PLK1 phosphorylation [].
PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone []. It is a key regulator of cytokinesis that cross-links antiparallel microtubules at an average distance of 35 nM [, ]. PRC1 is also required for KIF14 (a kinesin-3 family motor protein) localisation to the central spindle and midbody [, , ]and is required to recruit PLK1 to the spindle. It stimulates PLK1 phosphorylation of RACGAP1/HsCyk-4 to allow recruitment of ECT2 to the central spindle [].
This domain is found at the C terminus of A-kinase anchor protein 2 (AKAP2). It includes the site where the regulatory subunits (RII) of protein kinase AII binds [].Besides AKAP2, proteins containing this domain include mitotic interactor and substrate of PLK1 (Misp) []and uncharacterised protein LOC113230.
This is a family of microtubule associated proteins, including MAP65 (MAP65-1/2/3/4/5/6/7/8/9) from Arabidopsis, Ase1 from yeast, and PRC1 from mammals.Ase1 is required for spindle elongation and stabilisation. It is cell cycle-regulated by anaphase promoting complex []. It is a potential Cdc28p substrate []. MAP65-1 plays a role in stabilising anti-parallel microtubules in the central spindle at anaphase to early cytokinesis. MAP65-1 is cell cycle regulated by phosphorylation [, , , , ].PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone []. It is a key regulator of cytokinesis that cross-links antiparallel microtubules at an average distance of 35 nM [, ]. PRC1 is also required for KIF14 (a kinesin-3 family motor protein) localisation to the central spindle and midbody [, , ]and is required to recruit PLK1 to the spindle. It stimulates PLK1 phosphorylation of RACGAP1/HsCyk-4 to allow recruitment of ECT2 to the central spindle [].
TEX14 is an inactive serine/threonine-protein kinase because the active site aspartic acid residue has been replaced. It localizes to germ cell intercellular bridges during spermatogenesis. In germ cell cytokinesis a permanent intercellular bridge connecting the daughter cells through a large cytoplasmic channel forms, unlike in somatic cells. This bridge does not form in TEX14 deficient mice and male mice are sterile []; female knockout mice are fertile []. TEX14 binds to CEP55, which is a stable component of the intercellular bridge, via a GPPX3Y motif and preventing proteins with a similar motif (such as ALIX and TSG101) from binding to CEP55 []. During mitosis, TEX14 is recruited to kinetochores by Plk1 and without TEX14, kinetochores are unable to bind other essential components leading to chromosome instability. Phosphorylation of TEX14 by Plk1 leads to its degradation, which is essential for metaphase-to-anaphase transition and chromosome segregation []. TEX14 contains ankyrin repeat-containing domains and a protein kinase domain.
This entry includes animal M-phase-specific PLK1-interacting protein (also known as TTDN1) and plant protein SICKLE. M-phase-specific PLK1-interacting protein (also known as TTD non-photosensitive 1 protein, TTDN1) co-localises with Plk1 at the centrosome in mitosis and the midbody during cytokinesis []. TTDN1 is phosphorylated by cyclin-dependent kinase 1 during mitosis and subsequently interacts with polo-like kinase 1 (PLK1) [, ]. It may play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis []. Mutations in the C7orf11 (TTDN1) gene has been linked to Trichothiodystrophy (TTD), a rare autosomal recessive disorder whose defining feature is brittle hair []. Protein SICKLE is required for development and abiotic stress tolerance, and is involved in microRNA biogenesis []and mRNA splicing []. SICKLE, also known as ROTUNDA 3, may contribute to plant development by phosphatase 2A-mediated regulation of auxin transporter recycling [].
This entry represents M-phase-specific PLK1-interacting protein and related uncharacterised sequences from vertebrates.M-phase-specific PLK1-interacting protein (also known as TTD non-photosensitive 1 protein, TTDN1) may play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis []. Its The subcellular location is regulated during cell cycle. During interphase, it is located in the nucleus. During mitosis, it is located at the centrosome and dispersed in the cytoplasm. During telophase, it is located in the midbody. It colocalizes with PLK1 at the centrosome in M phase [, ]. It is phosphorylated during mitosis in the cell cycle probably by CDK1 [, ]. Defects in MPLKIP are a cause of trichothiodystrophy non-photosensitive type 1 (TTDN1); also known as Amish brittle hair brain syndrome (ABHS), hair-brain syndrome and BIDS syndrome. TTDN1 is an autosomal recessive disorder characterised by short stature, intellectual impairment, sulfur-deficient brittle hair and decreased male fertility but not cutaneous photosensitivity [].
This represents the mitotic checkpoint serine/threonine-protein kinase Bub1. Saccharomyces cerevisiae Bub1 has a paralogue, Mad3, which is also included in this entry. Bub1 forms a complex with Mad1 and Bub3 that is crucial for preventing cell cycle progression into anaphase in the presence of spindle damage [], while Mad3 is a component of the spindle-assembly complex consisting of Mad2, Mad3, Bub3 and Cdc20 []. Mad3 contains a D-box and two KEN- boxes, which function together to mediate Cdc20-Mad3 interaction. Mad3 and an anaphase-promoting complex (APC) substrate, Hsl1, compete for Cdc20 binding in a D-box- and KEN-box-dependent manner [].Similar to its yeast homologues, human Bub1 is a critical component of the mitotic checkpoint that delays the onset of anaphase until all chromosomes have established bipolar attachment to the microtubules. In interphase cells it localises to centrosomes and suppresses centrosome amplification via regulating Plk1 activity []. Mutations in the human Bub1 gene have been linked to cancers [, ].
Serine/Threonine Kinases (STKs) catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Polo-like kinases (PLKs) are serine/threonine kinases that play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes [].PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase [, , ]. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations []. PLK1 is overexpressed in many human cancers and is associated with poor prognosis [, , ].This entry represents the N-terminal catalytic kinase domain of PLK1.
