PRC1

Protein Regulator of cytokinesis 1 (PRC1) is a is_associated_with::protein that in humans is encoded by the PRC1 is_associated_with::gene and is involved in is_associated_with::cytokinesis.

Function
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 is_associated_with::interphase, becomes associated with the mitotic spindle in a highly dynamic manner during anaphase, and localizes to the cell midbody during cytokinesis. Shown to be a substrate of several is_associated_with::cyclin-dependent kinases (CDKs), PRC1 has become a novel human protein of cytokinetic importance since its identification in 1998. Correspondingly, ablation of PRC1 has been shown to disrupt spindle midzone assembly in mammalian systems.

At least three alternatively spliced transcript variants encoding distinct isoforms of PRC1 have been observed. Additionally, PRC1 has sequence homology with Ase1 in yeasts, SPD-1 (spindle defective 1) in C. elegans, Feo in is_associated_with::D. melanogaster, and MAP65 in plants, all of which fall in a conserved family of nonmotor is_associated_with::microtubule-associated proteins (MAPs).

Structure
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 is_associated_with::spectrin microtubule-binding domain, an extended rod domain, and an N-terminal dimerization domain. 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 is_associated_with::actin.

Role in cytokinesis
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. 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.

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. This PRC1-Kinesin-4 complex differentially identifies and regulates the spindle midzone microtubules during cell division. This regulation is crucial in order for cytokinesis to progress properly.

Interactions
PRC1 has been shown to interact with is_associated_with::TRIM37.


 * PRC1 forms a complex with Kinesin-4 that plays an important role in crossing spindle microtubules and setting midzone length in mammalian cytokinesis.
 * PRC1 is negatively modulated by CDKs, particularly is_associated_with::CDK1.
 * is_associated_with::PLK1 negatively regulates PRC1 through is_associated_with::phosphorylation at Thr-602, near the is_associated_with::C-terminus of PRC1, only after dephosphorylation of PRC1 at an inhibitory CDK1 site.
 * Kinesin-6 binds at the N-terminal half of PRC1.