Disease relevance of PRC1

• Site-specific expression of polycomb-group genes encoding the HPC-HPH/PRC1 complex in clinically defined primary nodal and cutaneous large B-cell lymphomas [1].
• Among the upregulated genes, we focused on the functional significance of protein regulator of cytokinesis 1 (PRC1) in the development of breast cancer [2].
• However, poorly differentiated DCIS and invasive carcinomas frequently expressed EZH2 in combination with HPC-HPH/PRC1 proteins [3].

High impact information on PRC1

• We find that PcG protein complexes PhoRC, PRC1, and PRC2 and the Trx protein are all constitutively bound to Polycomb response elements (PREs) in the OFF and ON state [4].
• We find that Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27 co-occupy >1000 silenced genes with a strong functional bias for embryonic development and cell fate decisions [5].
• Ring1B and Bmi1 are RING finger proteins that are members of the Polycomb repressive complex 1 (PRC1) [6].
• Here, we demonstrate that the chromodomain-containing protein, CBX8, which is part of one of the PRC1 complexes, regulates proliferation of diploid human and mouse fibroblasts through direct binding to the INK4A-ARF locus [7].
• We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis [8].

Biological context of PRC1

• PRC1 contains two Cdk phosphorylation motifs, and phosphorylation is possibly important to mitotic suppression of bundling, as a Cdk phosphorylation-null mutant causes extensive bundling of the prometaphase spindle [9].
• We demonstrate that PRC1, a mitotic spindle-associated Cdk substrate that is essential to cell cleavage, is a microtubule binding and bundling protein both in vivo and in vitro [9].
• Overexpression of PRC1 extensively bundles interphase microtubules, but does not affect early mitotic spindle organization [9].
• Truncation mutants demonstrate that the NH2-terminal region of PRC1, rich in alpha-helical sequence, is important for localization to the cleavage furrow and to the center of the midbody, whereas the central region, with the highest sequence homology between species, is required for microtubule binding and bundling activity [9].
• Polycomb group proteins Ring1b and Bmi1 (B-cell-specific Moloney murine leukaemia virus integration site 1) are critical components of the chromatin modulating PRC1 complex [10].

Anatomical context of PRC1

• In KIF4-deficient cells, the central spindle was disorganized, and all midzone-associated proteins including PRC1 failed to concentrate at the midline, instead being dispersed along the loosened microtubule bundles of the central spindle [11].
• These data provide a foundation for understanding the critical enzymatic activity at the core of the PRC1 polycomb complex, which is implicated in stem cell maintenance and cancer [10].
• We have examined the role of PRC1, a midzone-associated, microtubule bundling, Cdk substrate protein, in regulating the spatiotemporal formation of the midzone in HeLa cells [12].
• Western blot analysis using breast cancer cell lines revealed a significant increase in endogenous PRC1 levels in G(2)/M phase [2].
• Therefore, for the first time, we are able to indicate a functional involvement of Prc1 during the meiotic prophase of male germ cells and a regulatory role of Scmh1 for Prc1, which involves sex chromosomes [13].

Associations of PRC1 with chemical compounds

• In addition, E2-induced expression of PCNA, PRC1, and bcl-2 were inhibited by mitochondrial blockers [14].

Physical interactions of PRC1

• Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation [11].
• Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase [15].

Regulatory relationships of PRC1

• By isolation and characterization of a 3 kb genomic fragment containing the 5'-flanking region and part of exon 1 of PRC1 gene, we demonstrate that p53 directly suppresses PRC1 gene transcription [16].

Other interactions of PRC1

• Thus, PRC1 is required for interaction of the two half-spindles and for localization of KIF4 and CENP-E [11].
• Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis [17].
• The in vivo interaction of p53 with PRC1 gene promoter is further demonstrated by chromatin immunoprecipitation assay [16].
• Chromatin immunoprecipitations confirmed the ternary complex formation within the context of the PRC1 at the Bmi1 target loci [18].
• We have identified Scmh1 as an indispensable component of the Prc1 [13].

Analytical, diagnostic and therapeutic context of PRC1

• Using time-lapse and immunofluorescence analysis, we have addressed the consequences of eliminating the central spindle by ablation of PRC1, a microtubule bundling protein that is critical to the formation of the central spindle [19].
• Using time-lapse video microscopy, RNA interference, 3D immunofluorescence reconstruction imaging, and rescue experiments, we demonstrate that the dephosphorylated form of PRC1 is essential for bundling antiparallel, nonkinetochore, interdigitating microtubules to establish the midzone that is necessary for cytokinesis [12].

References