NHK-1 phosphorylates BAF to allow karyosome formation in the <i>Drosophila</i> oocyte nucleus

Lancaster, Oscar M.; Cullen, C. Fiona; Ohkura, Hiroyuki

doi:10.1083/jcb.200706067

Cited by 103 publications

(141 citation statements)

References 32 publications

(57 reference statements)

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“…However, it is not clear whether this has any relevance to the function of Ball in Drosophila muscle. The VRK family of kinases (of which Ball is a member) phosphorylate the barrier-to-autointegration factor (BAF), which is necessary for the correct assembly of chromatin (Gorjánácz et al, 2007;Lancaster et al, 2007;Margalit et al, 2007;Nichols et al, 2006). Comparison of domains in the sequences of Drosophila Ball (also called NHK-1) and VRK in human, mouse, Xenopus and C. elegans, shows that C. elegans and Drosophila are the only homologues with a long C-terminal sequence extension; the other species have a relatively short stretch of sequence following the kinase domain (Aihara et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…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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“…The N-terminal phosphorylation of BAF has been reported to cause the detachment of chromatin from the nuclear envelope during karyosome formation in the meiosis of the oocyte in Drosophila (Lancaster et al, 2007). The BAF N-terminus has three potential phosphorylation sites, including serine 2, threonine 4 and serine 5.…”

Section: Phosphorylation Of Baf Specifically Mediates Necrotic Pyknosismentioning

confidence: 99%

Necrotic pyknosis is a morphologically and biochemically distinct event from apoptotic pyknosis

Hou

et al. 2016

Journal of Cell Science

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Classification of apoptosis and necrosis by morphological differences has been widely used for decades. However, this usefulness of this method has been seriously questioned in recent years, mainly due to a lack of functional and biochemical evidence to interpret the morphology changes. To address this matter, we devised genetic manipulations in Drosophila to study pyknosis, a process of nuclear shrinkage and chromatin condensation that occurs in apoptosis and necrosis. By following the progression of necrotic pyknosis, we surprisingly observed a transient state of chromatin detachment from the nuclear envelope, followed by the nuclear envelope completely collapsing onto chromatin. This phenomenon led us to discover that phosphorylation of barrier-to-autointegration factor (BAF) mediates this initial separation of nuclear envelope from chromatin. Functionally, inhibition of BAF phosphorylation suppressed necrosis in both Drosophila and human cells, suggesting that necrotic pyknosis is conserved in the propagation of necrosis. In contrast, during apoptotic pyknosis the chromatin did not detach from the nuclear envelope and inhibition of BAF phosphorylation had no effect on apoptotic pyknosis and apoptosis. Our research provides the first genetic evidence supporting a morphological classification of apoptosis and necrosis through different forms of pyknosis.

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“…Elevated levels of VRK1 protein have been observed in highly proliferative cell lines, indicating its role in cell division (14). Furthermore, VRK1 is a nuclear protein, known to play an important role in cell cycle progression through phosphorylation of barrier to autointegration factor (15-17), which helps in formation of the nuclear envelope during cell division (18,19) and in the chromatin condensation event during cell division by phosphorylating histone H3 both at threonine 3 and serine 10 residues (20, 21).…”

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confidence: 99%

NMR Solution Structure of Human Vaccinia-related Kinase 1 (VRK1) Reveals the C-terminal Tail Essential for Its Structural Stability and Autocatalytic Activity

Shin

Chakraborty

Bharatham

et al. 2011

Journal of Biological Chemistry

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Vaccinia-related kinase 1 (VRK1) is one of the mitotic kinases that play important roles in cell cycle, nuclear condensation, and transcription regulation. Kinase domain structures of two other VRK family members (VRK2 and VRK3) have been determined previously. However, the structure of VRK1, the most extensively studied and constitutively active VRK member, is yet to be characterized. Here, we present the nuclear magnetic resonance (NMR) solution structure of a catalytically active form of human VRK1 with its extended C-terminal tail (residues 1-361). The NMR structure of human VRK1 reveals that the C-terminal tail orients toward the catalytic site and forms a number of interactions that are critical for structural stability and catalysis. The role of this unique C-terminal tail was further investigated by deletion mutant studies where deletion of the terminal tail resulted in a dramatic reduction in the autocatalytic activity of VRK1. NMR titration studies carried out with ATP or an ATP analog confirm that ATP/ATP analogs interact with all of the crucial residues present in important motifs of the protein kinase such as the hinge region, catalytic loop, DYG motif, and thereby suggest that the catalytic domain of VRK1 is not atypical. In addition to the conventional interactions, some of the residues present on the extended C-terminal tail also interact with the ligands. These observations also substantiate the role of the extended C-terminal tail in the biological activity of VRK1.The coordinated action of protein kinases and phosphatases plays a major role in regulating signal transduction events in a multicellular organism (1-3). Kinases comprise one of the major members of the human genome (4), characterized by the presence of a conserved catalytic domain of approximately 300 amino acids which is involved in the phosphotransfer reactions (5-7). Vaccinia-related kinase 1 (VRK1) 4 belongs to a novel group of serine/threonine kinases that bear a high degree of sequence similarity with vaccinia virus B1 R kinase (8, 9). Three members of VRK family are known in the human genome and show a significant sequence similarity among themselves with respect to their catalytic domains, but differ in their regulatory domains (8, 10). VRK1 is the most well studied member of the family, known to participate in a number of biological activities especially in cellular proliferations as well as in management of cellular stress situations (11). A number of studies demonstrated that VRK1 phosphorylates several stress-related transcription factors e.g. p53, c-Jun, ATF2, which in turn play a major role in regulating cellular fate (10 -12).Several studies have also reported the role of VRK1 in cellular proliferation both in normal cells as well as in cells with uncontrolled proliferation (13). Elevated levels of VRK1 protein have been observed in highly proliferative cell lines, indicating its role in cell division (14). Furthermore, VRK1 is a nuclear protein, known to play an important role in cell cycle progression through phosph...

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NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte nucleus

Cited by 103 publications

References 32 publications

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

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

Necrotic pyknosis is a morphologically and biochemically distinct event from apoptotic pyknosis

NMR Solution Structure of Human Vaccinia-related Kinase 1 (VRK1) Reveals the C-terminal Tail Essential for Its Structural Stability and Autocatalytic Activity

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