Survivin Reads Phosphorylated Histone H3 Threonine 3 to Activate the Mitotic Kinase Aurora B

Kelly, Alexander E.; Ghenoiu, Cristina; Xue, John Z.; Zierhut, Christian; Kimura, Hiroshi; Funabiki, Hironori

doi:10.1126/science.1189505

Cited by 444 publications

(506 citation statements)

References 23 publications

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“…These included: MIS18BP1, NSL1, CENP-E, CENP-F, Hec1, Borealin, and INCENP (supplemental Table S2-S3) as well as BUB1 and Aurora B kinases and, the BUBR1 pseudokinase. As expected, we observed down-regulation of phospho-sites on three of the four-chromosome passenger complex (CPC) protein subunits identified in this study: Aurora B, Borealin, and INCENP (9,39). These data are consistent with the notion that the absence of H3Thr 3ph caused by 5-ITu treatment reduces both Aurora B localization at the centromere and the localization of the other subunits of the CPC complex (Fig.…”

Section: Generation Of a Data Set Of Haspin Modulated Chromatin Assosupporting

confidence: 80%

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Modulation of the Chromatin Phosphoproteome by the Haspin Protein Kinase

Maiolica

Medina-Redondo

Schoof

et al. 2014

Molecular & Cellular Proteomics

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Recent discoveries have highlighted the importance of Haspin kinase activity for the correct positioning of the kinase Aurora B at the centromere. Haspin phosphorylates Thr 3 of the histone H3 (H3), which provides a signal for Aurora B to localize to the centromere of mitotic chromosomes. To date, histone H3 is the only confirmed Haspin substrate. We used a combination of biochemical, pharmacological, and mass spectrometric approaches to study the consequences of Haspin inhibition in mitotic cells. We quantified 3964 phosphorylation sites on chromatin-associated proteins and identified a Haspin protein-protein interaction network. We determined the Haspin consensus motif and the co-crystal structure of the kinase with the histone H3 tail.

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Section: Generation Of a Data Set Of Haspin Modulated Chromatin Assosupporting

confidence: 80%

“…1C) was not affected. This was probably because of incomplete Aurora B delocalization from the centromeres (9,11,12,39).…”

Section: Generation Of a Data Set Of Haspin Modulated Chromatin Assomentioning

confidence: 99%

Modulation of the Chromatin Phosphoproteome by the Haspin Protein Kinase

Maiolica

Medina-Redondo

Schoof

et al. 2014

Molecular & Cellular Proteomics

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“…Recently, it was reported that phosphorylation of histone H3 threonine 3 (H3T3ph) by Haspin is required for recruiting Aurora B protein kinase, an enzyme essential for accurate chromosome inheritance, to chromosomes that are poised to segregate into daughter cells (41,42). In addition, phosphorylation at threonine 6 (H3T6ph) by PKC␤ I plays a key role in preventing LSD1 from demethylating H3K4 but not from demethylating H3K9 during AR-dependent gene activation (43).…”

Section: Volume 286 • Number 42 • October 21 2011mentioning

confidence: 99%

Recognition of Unmodified Histone H3 by the First PHD Finger of Bromodomain-PHD Finger Protein 2 Provides Insights into the Regulation of Histone Acetyltransferases Monocytic Leukemic Zinc-finger Protein (MOZ) and MOZ-related factor (MORF)

Jin

Zhang

et al. 2011

Journal of Biological Chemistry

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MOZ (monocytic leukemic zinc-finger protein) and MORF (MOZ-related factor) are histone acetyltransferases important for HOX gene expression as well as embryo and postnatal development. They form complexes with other regulatory subunits through the scaffold proteins BRPF1/2/3 (bromodomain-PHD (plant homeodomain) finger proteins 1, 2, or 3). BRPF proteins have multiple domains, including two PHD fingers, for potential interactions with histones. Here we show that the first PHD finger of BRPF2 specifically recognizes the N-terminal tail of unmodified histone H3 (unH3) and report the solution structures of this PHD finger both free and in complex with the unH3 peptide. Structural analysis revealed that the unH3 peptide forms a third antiparallel ␤-strand that pairs with the PHD1 two-stranded antiparallel ␤-sheet. The binding specificity was determined primarily through the recognition of arginine 2 and lysine 4 of the unH3 by conserved aspartic acids of PHD1 and of threonine 6 of the unH3 by a conserved asparagine. Isothermal titration calorimetry and NMR assays showed that post-translational modifications such as H3R2me2as, H3T3ph, H3K4me, H3K4ac, and H3T6ph antagonized the interaction between histone H3 and PHD1. Furthermore, histone binding by PHD1 was important for BRPF2 to localize to the HOXA9 locus in vivo. PHD1 is highly conserved in yeast NuA3 and other histone acetyltransferase complexes, so the results reported here also shed light on the function and regulation of these complexes.Histone acetyltransferases (HATs) 3 are enzymes that catalyze the transfer of an acetyl group from acetyl-CoA to the ⑀-amino groups of lysine on histones, which results in important regulatory effects in chromatin structure and assembly as well as gene expression. HATs are highly diverse and generally form multiprotein complexes. Different HAT complexes are composed of various unique subunits, and the combination of these subunits contributes to the unique features of each HAT complex (1).MOZ (monocytic leukemic zinc-finger protein) and MORF (MOZ-related factor), a pair of large HATs of the MYST (Moz, Ybf2/Sas3, Sas2, Tip60) family, are important for hematopoiesis, skeletogenesis, neurogenesis, and other developmental processes, and they also have been implicated in leukemogenic and other tumorigenic progressions (2). A recent study in mice embryos reported that MOZ is required for normal levels of spatially correct Hox gene expression and for correct body segment identity. MOZ is specifically required for the H3K9 acetylation of active Hox gene loci (3). MOZ is also required for the maintenance of hematopoietic stem cells and plays a role in the differentiation of erythroid and myeloid cells (4). By contrast, MORF is required for the maintenance of undifferentiated neuronal progenitors and for adult neural stem cell self-renewal and neuronal differentiation (5). MOZ and MORF genes are often translocated in acute myeloid leukemia cells, producing either fusion proteins with CBP (cAMP-response elementbinding protein (CREB)-bind...

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“…This process was repeated with a second primary and secondary antibody for dual-labeling. Mitotic cells were visualized by Phospho-histone H3 (PHH3) labeling (50,51), and apoptotic nuclei by TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling) labeling performed according to the manufacturer's instructions (Roche, Indianapolis, IN). Peanut agglutinin (PNA) labeling was used to label the cone insoluble extracellular matrix domain (29), and done by incubating tissue sections in fluorescently-tagged PNA for 1 hour.…”

Section: Anatomic and Immunohistochemical Studiesmentioning

confidence: 99%

Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused byNPHP5mutation

et al. 2016

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Ciliary defects can result in severe disorders called ciliopathies. Mutations in NPHP5 cause a ciliopathy characterized by severe childhood onset retinal blindness, Leber congenital amaurosis (LCA), and renal disease. Using the canine NPHP5-LCA model we compared human and canine retinal phenotypes, and examined the early stages of photoreceptor development and degeneration, the kinetics of photoreceptor loss, the progression of degeneration and the expression profiles of selected genes. NPHP5-mutant dogs recapitulate the human phenotype of very early loss of rods, and relative retention of the central retinal cone photoreceptors that lack function. In mutant dogs, rod and cone photoreceptors have a sensory cilium, but develop and function abnormally and then rapidly degenerate; L/M cones are more severely affected than S-cones. The lack of outer segments in mutant cones indicates a ciliary dysfunction. Genes expressed in mutant rod or both rod and cone photoreceptors show significant downregulation, while those expressed only in cones are unchanged. Many genes in celldeath and -survival pathways also are downregulated. The canine disease is a non-syndromic LCA-ciliopathy, with normal renal structures and no CNS abnormalities. Our results identify the critical time points in the pathogenesis of the photoreceptor disease, and bring us closer to defining a potential time window for testing novel therapies for translation to patients. †

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Survivin Reads Phosphorylated Histone H3 Threonine 3 to Activate the Mitotic Kinase Aurora B

Cited by 444 publications

References 23 publications

Modulation of the Chromatin Phosphoproteome by the Haspin Protein Kinase

Modulation of the Chromatin Phosphoproteome by the Haspin Protein Kinase

Recognition of Unmodified Histone H3 by the First PHD Finger of Bromodomain-PHD Finger Protein 2 Provides Insights into the Regulation of Histone Acetyltransferases Monocytic Leukemic Zinc-finger Protein (MOZ) and MOZ-related factor (MORF)

Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused byNPHP5mutation

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