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| Aliases | PRC1 , ASE1, protein regulator of cytokinesis 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 603484 MGI: 1858961 HomoloGene: 37868 GeneCards: PRC1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Protein Regulator of cytokinesis 1 (PRC1) is a protein that in humans is encoded by the PRC1 gene and is involved in cytokinesis. [5] [6]
PRC1 protein is expressed at relatively high levels during S and G2/M phases of the cell cycle before dropping dramatically after mitotic exit and entrance into G1 phase. PRC1 is located in the nucleus during interphase, becomes associated with the mitotic spindle in a highly dynamic manner during anaphase, and localizes to the cell midbody during cytokinesis. PRC1 was first identified in 1998 using an ''in vitro'' phosphorylation screening method and shown to be a substrate of several cyclin-dependent kinases (CDKs). [5] Correspondingly, ablation of PRC1 has been shown to disrupt spindle midzone assembly in mammalian systems. [7]
At least three alternatively spliced transcript variants encoding distinct isoforms of PRC1 have been observed. [6] Additionally, PRC1 has sequence homology with Ase1 in yeasts, SPD-1 (spindle defective 1) in C. elegans, Feo in D. melanogaster, and MAP65 in plants, all of which fall in a conserved family of nonmotor microtubule-associated proteins (MAPs). [8] [9] [10]
The crystal structure of PRC1 has only recently been characterized in vitro. In 2013, PRC1 was illustrated as a lengthy molecule consisting of a C-terminal spectrin microtubule-binding domain, an extended rod domain, and an N-terminal dimerization domain. [9] [11] Consisting of an intricate arrangement of α-helices, the rod domain, together with the dimerization-conducting N terminus cooperate to facilitate binding of other proteins, such as Kinesin-4, to PRC1. PRC1’s rod domain adopts multiple conformations, all affected by its C-terminal spectrin domain. A model has been suggested in which PRC1 is likely to be a flexible molecule both in solution and on single microtubules but becomes more rigid when the microtubule-binding domains are restricted with antiparallel microtubule filament crosslinking, seen at the spindle midzone. The overall structure of the PRC1 homodimer is reminiscent of actin-bundling proteins, and this process of microtubule filament crosslinking is similar to that of actin. [9]
PRC1’s role in midzone microtubule formation, essential to the cytokinetic machinery of mammals, is made possible through its collaboration with Kinesin-4 in setting up a controlled zone of overlapping, antiparallel microtubules at the spindle midzone. [12] PRC1 is normally inhibited until anaphase onset by CDK1 mediated phosphorylation, preventing its dimerization. Upon anaphase onset and removal of inhibitory CDK1 phosphorylation, PRC1 dimers form. These homodimers specifically recognize antiparallel microtubule overlaps, found at the spindle midzone, and bind, allowing microtubule sliding, cross-linking of microtubule filaments, and assembly of central-spindle-mediating proteins, including but not limited to Kinesin-4. [12] [13]
PRC1 dimers, required for the high-affinity interaction with Kinesin-4, recruit Kinesin-4 to regions of antiparallel microtubule overlap, where Kinesin-4, a plus-end directed motor protein that inhibits microtubule dynamics, helps to form length-dependent end tags that help stabilize and regulate spindle microtubule assembly within cytokinesis. [9] [12] This PRC1-Kinesin-4 complex differentially identifies and regulates the spindle midzone microtubules during cell division. [12] This regulation is crucial in order for cytokinesis to progress properly.
Cytokinesis is the part of the cell division process and part of mitosis during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meiosis. During cytokinesis the spindle apparatus partitions and transports duplicated chromatids into the cytoplasm of the separating daughter cells. It thereby ensures that chromosome number and complement are maintained from one generation to the next and that, except in special cases, the daughter cells will be functional copies of the parent cell. After the completion of the telophase and cytokinesis, each daughter cell enters the interphase of the cell cycle.
In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.
The phragmoplast is a plant cell specific structure that forms during late cytokinesis. It serves as a scaffold for cell plate assembly and subsequent formation of a new cell wall separating the two daughter cells. The phragmoplast can only be observed in Phragmoplastophyta, a clade that includes the Coleochaetophyceae, Zygnematophyceae, Mesotaeniaceae, and Embryophyta. Some algae use another type of microtubule array, a phycoplast, during cytokinesis.
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.
The LIM kinases are a family of actin-binding kinases that phosphorylate members of the ADF/cofilin family of actin binding and filament severing proteins. The LIM kinase family is made up of two proteins: LIM kinase-1 (LIMK1) and LIM kinase-2 (LIMK2)
Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.
Polo-like kinases (Plks) are regulatory serine/threonine kinases of the cell cycle involved in mitotic entry, mitotic exit, spindle formation, cytokinesis, and meiosis. Only one Plk is found in the genomes of the fly Drosophila melanogaster (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates and other animals, however, have many Plk family members including Plk1, Plk2/Snk, Plk3/Prk/FnK, Plk4/Sak and Plk5. Of the vertebrate Plk family members, the mammalian Plk1 has been most extensively studied. During mitosis and cytokinesis, Plks associate with several structures including the centrosome, kinetochores, and the central spindle.
Kinesin-like protein KIF23 is a protein that in humans is encoded by the KIF23 gene.
Centromere-associated protein E is a protein that in humans is encoded by the CENPE gene.
Targeting protein for Xklp2 is a protein that in humans is encoded by the TPX2 gene. It is one of the many spindle assembly factors that play a key role in inducing microtubule assembly and growth during M phase.
Kinesin family member 4A is a protein that in humans is encoded by the KIF4A gene.
Kinesin-like protein KIF2C is a protein that in humans is encoded by the KIF2C gene.
Kinesin-like protein KIF20A is a protein that in humans is encoded by the KIF20A gene.
Centrosomal protein of 55 kDa(Cep55), is a protein that in humans is encoded by the CEP55 gene.
Kinesin-like protein KIFC1 is a protein that in humans is encoded by the KIFC1 gene.
Cdc14 and Cdc14 are a gene and its protein product respectively. Cdc14 is found in most of the eukaryotes. Cdc14 was defined by Hartwell in his famous screen for loci that control the cell cycle of Saccharomyces cerevisiae. Cdc14 was later shown to encode a protein phosphatase. Cdc14 is dual-specificity, which means it has serine/threonine and tyrosine-directed activity. A preference for serines next to proline is reported. Many early studies, especially in the budding yeast Saccharomyces cerevisiae, demonstrated that the protein plays a key role in regulating late mitotic processes. However, more recent work in a range of systems suggests that its cellular function is more complex.
Mitotic exit is an important transition point that signifies the end of mitosis and the onset of new G1 phase for a cell, and the cell needs to rely on specific control mechanisms to ensure that once it exits mitosis, it never returns to mitosis until it has gone through G1, S, and G2 phases and passed all the necessary checkpoints. Many factors including cyclins, cyclin-dependent kinases (CDKs), ubiquitin ligases, inhibitors of cyclin-dependent kinases, and reversible phosphorylations regulate mitotic exit to ensure that cell cycle events occur in correct order with fewest errors. The end of mitosis is characterized by spindle breakdown, shortened kinetochore microtubules, and pronounced outgrowth of astral (non-kinetochore) microtubules. For a normal eukaryotic cell, mitotic exit is irreversible.
Kinesin-like protein KIF11 is a molecular motor protein that is essential in mitosis. In humans it is coded for by the gene KIF11. Kinesin-like protein KIF11 is a member of the kinesin superfamily, which are nanomotors that move along microtubule tracks in the cell. Named from studies in the early days of discovery, it is also known as Kinesin-5, or as BimC, Eg5 or N-2, based on the founding members of this kinesin family.
Kinesin family member 15 is a protein that in humans is encoded by the KIF15 gene.
Centralspindlin is a motor complex implicated in cell division. It contributes to virtually every step in cytokinesis, It is highly conserved in animal cells as a component of the spindle midzone and midbody. Centralspindlin is required for the assembly of the mitotic spindle as well as for microtubule bundling and anchoring of midbody microtubules to the plasma membrane. This complex is also implicated in tethering the spindle apparatus to the plasma membrane during cytokinesis This interaction permits cleavage furrow ingression. In addition, centralspindlin's interaction with the ESCRT III allows for abscission to occur.
