Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early <i>Drosophila</i> embryo

Aihara, Hitoshi; Nakagawa, Takeya; Yasui, Kiyoshi; Ohta, Tsutomu; Hirose, Susumu; Dohmae, Naoshi; Takio, Koji; Kaneko, Mayumi; Takeshima, Yukio; Muramatsu, Masami; Ito, Takashi

doi:10.1101/gad.1184604

Cited by 93 publications

(129 citation statements)

References 39 publications

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“…Later the unique Drosophila melanogaster ortholog of this human kinase family, the NHK-1 (nucleosomal histone kinase), has also been shown to phosphorylate histones and is essential for chromosome condensation and mitotic progression (47)(48)(49)(50). Histone H3 plays an important role in chromatin condensation once the DNA synthesis has 3 H]GDP followed by incubation with the specified amounts of RCC1 for 5 min and 2 mM GTP without VRK1 or with different amounts of VRK1.…”

Section: Discussionmentioning

confidence: 99%

Proteomics Identification of Nuclear Ran GTPase as an Inhibitor of Human VRK1 and VRK2 (Vaccinia-related Kinase) Activities

Sanz-García¹,

López-Sánchez²,

Lazo

2008

Molecular & Cellular Proteomics

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Human vaccinia-related kinase (VRK) 1 is a novel serinethreonine kinase that regulates several transcription factors, nuclear envelope assembly, and chromatin condensation and is also required for cell cycle progression. The regulation of this kinase family is unknown. Mass spectrometry has permitted the identification of Ran as an interacting and regulatory protein of the VRK serine-threonine kinase activities. The stable interaction has been validated by pulldown of endogenous proteins as well as by reciprocal immunoprecipitations. The three members of the VRK family stably interact with Ran, and the interaction was not affected by the bound nucleotide, GDP or GTP. The interaction was stronger with the RanT24N that is locked in its inactive conformation and cannot bind nucleotides. None of the kinases phosphorylated Ran or RCC1. VRK1 does not directly interact with RCC1, but if Ran is present they can be isolated as a complex. The main effect of the interaction of inactive RanGDP with VRK1 is the inhibition of its kinase activity, which was detected by a reduction in VRK1 autophosphorylation and a reduction in phosphorylation of histone H3 in residues Thr-3 and Ser-10. The kinase activity inhibition can be relieved by the interaction with the constitutively active RanGTP or RanL43E, which locks Ran in its GTP-bound active conformation. In this complex, the interaction with VRK proteins does not alter the effect of its guanine exchange factor, RCC1. Ran is a novel negative regulator of nuclear VRK1 and VRK2 kinase activity, which may vary in different subcellular localizations generating an asymmetric intracellular distribution of kinase activity depending on local protein interactions.

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Section: Discussionmentioning

confidence: 99%

Proteomics Identification of Nuclear Ran GTPase as an Inhibitor of Human VRK1 and VRK2 (Vaccinia-related Kinase) Activities

Sanz-García¹,

López-Sánchez²,

Lazo

2008

Molecular & Cellular Proteomics

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“…1B and supplementary material Table S1). Unlike Kin1 and Kin2, Ball is predicted to be an active kinase homologous to the vaccinia-related kinases (VRKs), which are found in all invertebrates and vertebrates (Aihara et al, 2004;Herzig et al, 2014;Lancaster et al, 2007) (supplementary material Fig. S1B).…”

Section: Identification Of Binding Partners Of Kin1mentioning

confidence: 99%

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

Katzemich

West

Fukuzawa

et al. 2015

Journal of Cell Science

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Drosophila obscurin (Unc-89) is a titin-like protein in the M-line of the muscle sarcomere. Obscurin has two kinase domains near the C-terminus, both of which are predicted to be inactive. We have identified proteins binding to the kinase domains. Kinase domain 1 bound Bällchen (Ball, an active kinase), and both kinase domains 1 and 2 bound MASK (a 400-kDa protein with ankyrin repeats). Ball was present in the Z-disc and M-line of the indirect flight muscle (IFM) and was diffusely distributed in the sarcomere. MASK was present in both the M-line and the Z-disc. Reducing expression of Ball or MASK by siRNA resulted in abnormalities in the IFM, including missing M-lines and multiple Z-discs. Obscurin was still present, suggesting that the kinase domains act as a scaffold binding Ball and MASK. Unlike obscurin in vertebrate skeletal muscle, Drosophila obscurin is necessary for the correct assembly of the IFM sarcomere. We show that Ball and MASK act downstream of obscurin, and both are needed for development of a well defined M-line and Z-disc. The proteins have not previously been identified in Drosophila muscle.

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“…(A) H3wt, cloned in pET11a (gift from James T. Kadonaga), was mutated into alanine(H3K4A), arginine(H3K4R), and glutamine(H3K4Q). The H3-H4 tetramer was expressed and purified, as shown in the lowest panel, basically as described previously (Aihara et al 2004). Chromatin was assembled using recombinant H3-H4 and native H2A-H2B, and was subjected to GAL4-VP16-mediated transcription.…”

Section: Ubiquitylation Of H2a Represses Transcriptional Initiation Bmentioning

confidence: 99%

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

Nakagawa

Kajitani²,

Togo³

et al. 2008

Genes Dev.

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206

229

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Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di-and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di-and trimethylation of H3K4, resulting in regulation of transcriptional initiation.[Keywords: Nucleosome; ubiquitylation; histone code; transcription; USP21; H2A] Supplemental material is available at http://www.genesdev.org.

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Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo

Cited by 93 publications

References 39 publications

Proteomics Identification of Nuclear Ran GTPase as an Inhibitor of Human VRK1 and VRK2 (Vaccinia-related Kinase) Activities

Proteomics Identification of Nuclear Ran GTPase as an Inhibitor of Human VRK1 and VRK2 (Vaccinia-related Kinase) Activities

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

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