Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P52742 (pT3)
 1,034 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For proper partitioning of chromosomes in mitosis, the chromosomal passenger complex (CPC) including Aurora B and survivin must be localized at the center of paired kinetochores, at the site called the inner centromere. It is largely unknown what defines the inner centromere and how the CPC is targeted to this site. Here, we show that the phosphorylation of histone H3-threonine 3 (H3-pT3) mediated by Haspin cooperates with Bub1-mediated histone 2A-serine 121 (H2A-S121) phosphorylation in targeting the CPC to the inner centromere in fission yeast and human cells. H3-pT3 promotes nucleosome binding of survivin, whereas phosphorylated H2A-S121 facilitates the binding of shugoshin, the centromeric CPC adaptor. Haspin colocalizes with cohesin by associating with Pds5, whereas Bub1 localizes at kinetochores. Thus, the inner centromere is defined by intersection of two histone kinases.
 ...
PMID:Two histone marks establish the inner centromere and chromosome bi-orientation. 2092 62

Successful partitioning of chromosomes in mitosis relies on the bipolar attachment of sister chromatids at metaphase. For this biorientation, the chromosomal passenger complex (CPC), composed of catalytic kinase Aurora B and regulatory components (INCENP, Survivin, and Borealin), must be localized at the center of paired kinetochores, the site called the inner centromere. It is largely unknown what defines the inner centromere and how the CPC is targeted to this site. Recent studies point out that the shugoshin protein (SGO), originally identified as a cohesin protector, also acts as a conserved centromeric adapter of the CPC. Phosphorylation of the CPC by Cdk1 promotes direct binding with shugoshin, thus explaining how the CPC is targeted to the centromere in a timely manner at prometaphase during the cell cycle. Moreover, the phosphorylation of histone H3 threonine 3 (H3-pT3) mediated by Haspin cooperates with Bub1-mediated H2A-S121 phosphorylation in targeting the CPC to the inner centromere. H3-pT3 promotes nucleosome binding of Survivin, whereas H2A-pS121 facilitates the binding of shugoshin. Haspin colocalizes with cohesin by associating with Pds5, a cohesin-binding protein, and Bub1 localizes at kinetochores. Thus, the inner centromere is defined by the spatial intersection of two histone marks mediated by cohesin- and kinetochore-associated kinases.
 ...
PMID:Temporal and spatial regulation of targeting aurora B to the inner centromere. 2144 16

It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression pattern of H3K27me3 and its clinicopathological/prognostic significance in urothelial carcinoma of bladder (UCB) are unclear. In this study, upregulated expression of H3K27me3 protein was observed in the majority of UCBs by Western blotting. High expression of H3K27me3 was examined by IHC in 59/126 (46.8%) of UCB tissues and in 18/72 (25.0%) of normal urothelial bladder epithelial tissues (P = 0.002). High expression of H3K27me3 was associated with multifocal tumors and lymph node metastases (P < 0.05). Patients with high expression of H3K27me3 had shorter cancer-specific survival (CSS) time than patients with low expression of H3K27me3 (P < 0.001). In different subsets of UCB patients, high expression of H3K27me3 was also a prognostic indicator in patients with grade 2 and grade 3, pT1, pT2, pT3, and pN- disease (P < 0.05). Importantly, expression of H3K27me3 was an independent predictor for CSS (P < 0.001) of UCB patients treated with radical cystectomy (RC). Our data suggests that high expression of H3K27me3 is an independent molecular marker for predicting poor prognosis of UCB patients treated with RC.
...
PMID:High expression of H3K27me3 is an independent predictor of worse outcome in patients with urothelial carcinoma of bladder treated with radical cystectomy. 2409 96

Sister-chromatid cohesion is established by the cohesin complex in S phase and persists until metaphase, when sister chromatids are captured by microtubules emanating from opposite poles [1]. The Aurora-B-containing chromosome passenger complex (CPC) plays a crucial role in achieving chromosome bi-orientation by correcting erroneous microtubule attachment [2]. The centromeric localization of the CPC relies largely on histone H3-T3 phosphorylation (H3-pT3), which is mediated by the mitotic histone kinase Haspin/Hrk1 [3-5]. Hrk1 localization to centromeres depends largely on the cohesin subunit Pds5 in fission yeast [5]; however, it is unknown how Pds5 regulates Hrk1 localization. Here we identify a conserved Hrk1-interacting motif (HIM) in Pds5 and a Pds5-interacting motif (PIM) in Hrk1 in fission yeast. Mutations in either motif result in the displacement of Hrk1 from centromeres. We also show that the mechanism of Pds5-dependent Hrk1 recruitment is conserved in human cells. Notably, the PIM in Haspin/Hrk1 is reminiscent of the YSR motif found in the mammalian cohesin destabilizer Wapl and stabilizer Sororin, both of which bind PDS5 [6-12]. Similarly, and through the same motifs, fission yeast Pds5 binds to Wpl1/Wapl and acetyltransferase Eso1/Eco1, in addition to Hrk1. Thus, we have identified a protein-protein interaction module in Pds5 that serves as a chromatin platform for regulating sister-chromatid cohesion and chromosome bi-orientation.
 ...
PMID:Pds5 Regulates Sister-Chromatid Cohesion and Chromosome Bi-orientation through a Conserved Protein Interaction Module. 2834 69