# PRC1

## Overview
The PRC1 gene encodes the protein regulator of cytokinesis 1, a microtubule-associated protein that plays a pivotal role in cell division by regulating the mitotic spindle midzone. This protein is essential for the proper bundling and stabilization of antiparallel microtubules during cytokinesis, ensuring accurate chromosome segregation and successful cell division (Zhu2006Spatiotemporal; Mollinari2002PRC1). PRC1 is characterized by its spectrin fold domain, which facilitates microtubule binding, and a dimerization domain that enables the crosslinking of microtubules (Tan2022NTerminusMediated; Subramanian2010Insights). The protein's activity is tightly regulated by phosphorylation, which modulates its function throughout the cell cycle (Mollinari2002PRC1). Dysregulation of PRC1 has been implicated in various pathological conditions, including cancer, where it affects cell proliferation and survival, highlighting its potential as a therapeutic target (van2016Noncanonical; Cohen2018PRC1).

## Structure
The PRC1 protein, or Protein Regulator of Cytokinesis 1, is a human microtubule-associated protein involved in antiparallel microtubule crosslinking. Its molecular structure includes several distinct domains that contribute to its function. The microtubule-binding domain of PRC1 is characterized by a spectrin fold, which is typically found in actin crosslinking proteins but has evolved in PRC1 to mediate microtubule binding (Subramanian2010Insights). This domain is complemented by a Lys/Arg-rich unstructured domain that enhances microtubule binding and is subject to phospho-regulation, affecting PRC1's microtubule affinity (Subramanian2010Insights).

The dimerization domain of PRC1 forms a U-shaped hairpin structure, creating a four-helix bundle upon dimerization, which is crucial for its function in crosslinking microtubules (Tan2022NTerminusMediated). The spectrin domain is highly ordered and less flexible compared to other domains when bound to a microtubule (Subramanian2010Insights). PRC1's structure allows it to selectively crosslink antiparallel microtubules with a narrow range of interfilament spacing, facilitated by the specific conformation of its dimerization domain (Subramanian2010Insights). The protein's ability to distinguish between parallel and antiparallel filaments relies on the spectrin domain's ordered binding to the microtubule lattice (Subramanian2010Insights).

## Function
PRC1 (protein regulator of cytokinesis 1) is a microtubule-binding and bundling protein that plays a critical role in maintaining the mitotic spindle midzone during cell division, which is essential for cytokinesis in human cells (Zhu2006Spatiotemporal; Mollinari2002PRC1). It is involved in the bundling of antiparallel, nonkinetochore, interdigitating microtubules to establish the midzone, a structure necessary for proper chromosome segregation and successful cell division (Zhu2006Spatiotemporal).

PRC1's activity is regulated by phosphorylation, which suppresses its bundling activity during early mitosis. This regulation is mediated by cyclin-dependent kinases (Cdks), and dephosphorylation in late mitosis reactivates PRC1 to stabilize the midzone microtubule bundles (Zhu2006Spatiotemporal; Mollinari2002PRC1). PRC1 interacts with other proteins, such as the kinesin motor protein Kif4, which translocates PRC1 along microtubules to the plus ends of interdigitating mitotic spindles (Zhu2006Spatiotemporal).

In the absence of PRC1, cells exhibit defects in spindle morphology and cytokinesis, leading to binucleated cells, highlighting its essential role in cell division (Zhu2006Spatiotemporal; Li2004Identification). PRC1's function is crucial for maintaining spindle architecture, spindle elongation, and cleavage furrow positioning, ensuring proper cell division and tissue maintenance (Zhu2006Spatiotemporal).

## Clinical Significance
Mutations and alterations in the expression of the PRC1 gene have significant clinical implications, particularly in the context of cancer. PRC1 is crucial for maintaining epidermal tissue integrity, and its loss can lead to skin disorders characterized by fragility and blistering, similar to human skin fragility syndromes (Cohen2018PRC1a). In leukemia, the non-canonical PRC1.1 complex, which includes PRC1, is essential for leukemic cell viability. Disruption of PRC1.1 components, such as through knockdown of its subunits, results in reduced proliferation and survival of leukemic cells, highlighting its potential as a therapeutic target (van2016Noncanonical).

PRC1 mutations or dysregulation can also impact skin development and stem cell specification. Loss of PRC1's catalytic activity affects gene repression and activation, leading to changes in the expression of genes critical for skin and hair follicle development (Cohen2018PRC1). This can result in phenotypic changes, such as an increase in Merkel cells, due to the altered expression of key developmental genes (Cohen2018PRC1). These findings underscore the importance of PRC1 in maintaining normal cellular functions and its role in disease pathogenesis when dysregulated.


## References


[1. (Zhu2006Spatiotemporal) Changjun Zhu, Eric Lau, Robert Schwarzenbacher, Ella Bossy-Wetzel, and Wei Jiang. Spatiotemporal control of spindle midzone formation by prc1 in human cells. Proceedings of the National Academy of Sciences, 103(16):6196–6201, April 2006. URL: http://dx.doi.org/10.1073/pnas.0506926103, doi:10.1073/pnas.0506926103. This article has 129 citations.](https://doi.org/10.1073/pnas.0506926103)

[2. (Cohen2018PRC1a) Idan Cohen, Dejian Zhao, Gopinathan Menon, Manabu Nakayama, Haruhiko Koseki, Deyou Zheng, and Elena Ezhkova. Prc1 preserves epidermal tissue integrity independently of prc2. Genes & Development, 33(1–2):55–60, December 2018. URL: http://dx.doi.org/10.1101/gad.319939.118, doi:10.1101/gad.319939.118. This article has 37 citations.](https://doi.org/10.1101/gad.319939.118)

[3. (Tan2022NTerminusMediated) Fei Tan and Jin Xu. N-terminus-mediated solution structure of dimerization domain of prc1. Current Issues in Molecular Biology, 44(4):1626–1645, April 2022. URL: http://dx.doi.org/10.3390/cimb44040111, doi:10.3390/cimb44040111. This article has 1 citations and is from a peer-reviewed journal.](https://doi.org/10.3390/cimb44040111)

[4. (Li2004Identification) Cong Li, Meihong Lin, and Jingwen Liu. Identification of prc1 as the p53 target gene uncovers a novel function of p53 in the regulation of cytokinesis. Oncogene, 23(58):9336–9347, November 2004. URL: http://dx.doi.org/10.1038/sj.onc.1208114, doi:10.1038/sj.onc.1208114. This article has 48 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1038/sj.onc.1208114)

[5. (van2016Noncanonical) Vincent van den Boom, Henny Maat, Marjan Geugien, Aida Rodríguez López, Ana M. Sotoca, Jennifer Jaques, Annet Z. Brouwers-Vos, Fabrizia Fusetti, Richard W.J. Groen, Huipin Yuan, Anton C.M. Martens, Hendrik G. Stunnenberg, Edo Vellenga, Joost H.A. Martens, and Jan Jacob Schuringa. Non-canonical prc1.1 targets active genes independent of h3k27me3 and is essential for leukemogenesis. Cell Reports, 14(2):332–346, January 2016. URL: http://dx.doi.org/10.1016/j.celrep.2015.12.034, doi:10.1016/j.celrep.2015.12.034. This article has 117 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1016/j.celrep.2015.12.034)

[6. (Subramanian2010Insights) Radhika Subramanian, Elizabeth M. Wilson-Kubalek, Christopher P. Arthur, Matthew J. Bick, Elizabeth A. Campbell, Seth A. Darst, Ronald A. Milligan, and Tarun M. Kapoor. Insights into antiparallel microtubule crosslinking by prc1, a conserved nonmotor microtubule binding protein. Cell, 142(3):433–443, August 2010. URL: http://dx.doi.org/10.1016/j.cell.2010.07.012, doi:10.1016/j.cell.2010.07.012. This article has 254 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1016/j.cell.2010.07.012)

[7. (Cohen2018PRC1) Idan Cohen, Dejian Zhao, Carmit Bar, Victor J. Valdes, Katherine L. Dauber-Decker, Minh Binh Nguyen, Manabu Nakayama, Michael Rendl, Wendy A. Bickmore, Haruhiko Koseki, Deyou Zheng, and Elena Ezhkova. Prc1 fine-tunes gene repression and activation to safeguard skin development and stem cell specification. Cell Stem Cell, 22(5):726-739.e7, May 2018. URL: http://dx.doi.org/10.1016/j.stem.2018.04.005, doi:10.1016/j.stem.2018.04.005. This article has 110 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1016/j.stem.2018.04.005)

[8. (Mollinari2002PRC1) Cristiana Mollinari, Jean-Philippe Kleman, Wei Jiang, Guy Schoehn, Tony Hunter, and Robert L. Margolis. Prc1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. The Journal of Cell Biology, 157(7):1175–1186, June 2002. URL: http://dx.doi.org/10.1083/jcb.200111052, doi:10.1083/jcb.200111052. This article has 371 citations.](https://doi.org/10.1083/jcb.200111052)