Protein Regulator of cytokinesis 1 (PRC1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''PRC1''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

and is involved in

cytokinesis Cytokinesis () is the part of the cell division process 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 mei ...

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 Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

during

interphase Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...

, 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 Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They ...

(CDKs). 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 ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

, Feo in

D. melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

, and MAP65 in plants, all of which fall in a conserved family of nonmotor

microtubule-associated proteins In cell biology, microtubule-associated proteins (MAPs) are proteins that interact with the microtubules of the cellular cytoskeleton. MAPs are integral to: the stability of the cell and its internal structures and the transport of components with ...

(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

spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membr ...

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

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

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 is a non-motor microtubule-associated protein (MAP) whose C-terminal spectrin domain (aa 341-640) binds microtubules with micromolar affinity (0.6 +/- 0.3uM) * PRC1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with TRIM37. * PRC1 interacts 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

CDK1 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in t ...

. *

PLK1 Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the ''PLK1'' ( polo-like kinase 1) gene. Structure PLK1 consists of 603 am ...

negatively regulates PRC1 through phosphorylation at Thr-602, near the C-terminus of PRC1, only after dephosphorylation of PRC1 at an inhibitory CDK1 site. * PRC1 binds directly to CYK-4 subunit of the centralspindlin complex to stabilise the central spindle.

References

External links