A novel ninein‐interaction protein, CGI‐99, blocks ninein phosphorylation by GSK3β and is highly expressed in brain tumors

Howng, Shen-Long; Hsu, Hui‐Chun; Cheng, Tsung Chieh; Lee, Yun-Lin; Chang, Li-Kwan; Lu, Pei‐Jung; Hong, Yi‐Ren

doi:10.1016/j.febslet.2004.04.024

Cited by 43 publications

(48 citation statements)

References 32 publications

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“…Phosphorylation by polo-like kinase 1 (Plk1) has been shown to be responsible for the release of nineinlike protein (Nlp) from the centrosome but this is not the case for ninein (Casenghi et al, 2005). However, GSK3␤, which is present at the centrosome, has been reported to phosphorylate ninein (Hong et al, 2000a;Hong et al, 2000b;Howng et al, 2004) and could potentially influence its association with the centrosome. We therefore investigated the affect of GSK3␤ inhibition on ninein release from the centrosome.…”

Section: Resultsmentioning

confidence: 99%

Ninein is released from the centrosome and moves bi-directionally along microtubules

Moss

Bellett

Carter

et al. 2007

Journal of Cell Science

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Cell-to-cell contact and polarisation of epithelial cells involve a major reorganisation of the microtubules and centrosomal components. The radial microtubule organisation is lost and an apico-basal array develops that is no longer anchored at the centrosome. This involves not only the relocation of microtubules but also of centrosomal anchoring proteins to apical non-centrosomal sites. The relocation of microtubule minus-end-anchoring proteins such as ninein to the apical sites is likely to be essential for the assembly and stabilisation of the apico-basal arrays in polarised epithelial cells. In this study, we establish that ninein is highly dynamic and that, in epithelial cells, it is present not only at the centrosome but also in the cytoplasm as distinct speckles. Live-cell imaging reveals that GFP-ninein speckles are released from the centrosome and move in a microtubule-dependent manner within the cytoplasm and thus establishes that epithelial cells possess the mechanical means for relocation of ninein to non-centrosomal anchoring sites. We also provide evidence for the deployment of ninein speckles to apical anchoring sites during epithelial differentiation in both an in situ tissue and an in vitro culture system. In addition, the findings suggest that the non-centrosomal microtubule anchoring sites associate with adherens junctions in polarised epithelial cells

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Section: Resultsmentioning

confidence: 99%

Ninein is released from the centrosome and moves bi-directionally along microtubules

Moss

Bellett

Carter

et al. 2007

Journal of Cell Science

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“…cDNAs encoding glutathione S-transferase (GST)-tagged truncated forms of mouse ninein (amino acids 1 to 246, 1 to 96, and 246 to 496) (GenBank/EMBL/DDJB accession number AY515727) were gifts from M. Bornens (Institute Curie, France) (30). cDNAs encoding GFP-tagged WT and mutant ninein (amino acids 1179 to 1931) and His-tagged mutant ninein (amino acids 1617 to 2090) (human isoform 5; accession number AAG33512.2) were gifts from Y. R. Hong (Kaohsiung Medical University, Taiwan) (36). Primary antibodies (Ab) used in this study were polyclonal anti-p1007/1008 Tyr-JAK2 (44426G) and monoclonal anti-JAK2 (Invitrogen), XP monoclonal rabbit anti-JAK2 (D2E12) (Cell Signaling), polyclonal anti-JAK1 and anti-Tyk2 (Santa Cruz Biotechnology, Inc.), monoclonal anti-␥-tubulin (GTU-88) (Sigma-Aldrich), polyclonal anti-␥-tubulin (Santa Cruz Biotechnology, Inc.), monoclonal anti-␤-tubulin (E7) (Developmental Studies Hybridoma Bank at the University of Iowa), polyclonal anticentrin (H-40) (Santa Cruz Biotechnology, Inc.), polyclonal anti-phospho-histone H3 (Ser10) (Cell Signaling), monoclonal antiphosphotyrosine (anti-PY) (clone 4G10; EMD Millipore).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, human ninein interacts with a novel centrosomal protein, CGI-99 (36), and the spindleassociated protein astrin (37). glycogen synthase kinase 3␤ (GSK3␤) Aurora A, and protein kinase A (PKA) phosphorylate the C terminus of ninein (36,38,39). Two coiled-coiled domains FIG 1 Active JAK2 tyrosine kinase localizes to the centrosome.…”

mentioning

confidence: 99%

“…Ninein interacts with the ␥-tubulin ring complexes and couples MT nucleation and anchoring at the centrosomes (30,33). In addition, human ninein interacts with a novel centrosomal protein, CGI-99 (36), and the spindleassociated protein astrin (37). glycogen synthase kinase 3␤ (GSK3␤) Aurora A, and protein kinase A (PKA) phosphorylate the C terminus of ninein (36,38,39).…”

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confidence: 99%

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JAK2 Tyrosine Kinase Phosphorylates and Is Negatively Regulated by Centrosomal Protein Ninein

Jay

Hammer

Nestor-Kalinoski

et al. 2015

Molecular and Cellular Biology

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JAK2 is a cytoplasmic tyrosine kinase critical for cytokine signaling. In this study, we have identified a novel centrosome-associated complex containing ninein and JAK2. We have found that active JAK2 localizes around the mother centrioles, where it partly colocalizes with ninein, a protein involved in microtubule (MT) nucleation and anchoring. We demonstrated that JAK2 is an important regulator of centrosome function. Depletion of JAK2 or use of JAK2-null cells causes defects in MT anchoring and increased numbers of cells with mitotic defects; however, MT nucleation is unaffected. We showed that JAK2 directly phosphorylates the N terminus of ninein while the C terminus of ninein inhibits JAK2 kinase activity in vitro. Overexpressed wild-type (WT) or C-terminal (amino acids 1179 to 1931) ninein inhibits JAK2. This ninein-dependent inhibition of JAK2 significantly decreases prolactin-and interferon gamma (IFN-␥)-induced tyrosyl phosphorylation of STAT1 and STAT5. Downregulation of ninein enhances JAK2 activation. These results indicate that JAK2 is a novel member of centrosome-associated complex and that this localization regulates both centrosomal function and JAK2 kinase activity, thus controlling cytokine-activated molecular pathways. JAK2 is a tyrosine kinase that is activated by two-thirds of the cytokine/hematopoietin receptor superfamily. JAK2 activation initiates a variety of downstream signaling events that lead to diverse physiological responses to cytokines, including regulation of body growth, hematopoiesis, satiety, lactation, and various immune functions. Upon activation, receptor-bound JAK2 phosphorylates specific tyrosine residues of its downstream targets, activating cell survival/proliferation-promoting signaling pathways (1). One target of JAK2 is a family of transcription factors termed signal transducers and activators of transcription (STATs). STATs exist within the cytoplasm in a latent or inactive state; they are recruited by cytokine receptor complexes through interaction between the receptor or JAK phosphotyrosines and the Src homology 2 (SH2) domain of the STAT protein. Several additional kinase cascades may be activated by JAK2, including phosphoinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Three mechanisms of JAK2 activation at the genetic level have been implicated in hematologic malignancies: point mutations, translocations, and amplifications (reviewed in reference 2). Mutations within the pseudokinase domain of JAK2 were detected in a spectrum of myeloproliferative diseases. A V617F gain-of-function point mutation is the cause of ϳ90% of all polycythemia vera cases and ϳ50% of all essential thrombocythemia and primitive myelofibrosis cases (3, 4). Several additional mutations leading to constitutively active JAK2 have been identified recently in patients, including a JAK2 K539L mutant. A T875N substitution in JAK2 was also identified in megakaryoblastic myeloid leukemia cells. In a patient with trisomy 21 and B cell precursor acute lymphoblastic l...

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“…C14orf166 is frequently detected during ciliogenesis since it has been reported by three other studies. This gene encodes protein involved in the functional regulation of human ninein in the centrosome structure [6][7][8]30]. It would be interesting to obtain complete data on C14orf166 and elucidate the biological function of C7orf49.…”

Section: Discussionmentioning

confidence: 99%

Identification of transcripts overexpressed during airway epithelium differentiation

Chhin

Pham²,

Zein³

et al. 2008

Eur Respir J

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Human airway epithelium, the defence at the forefront of protecting the respiratory tract, evacuates inhaled particles by a permanent beating of epithelial cell cilia. When deficient, this organelle causes primary ciliary dyskinesia, and, despite numerous studies, data regarding ciliated cell gene expression remain incomplete. The aim of the present study was to identify genes specifically expressed in human ciliated respiratory cells via transcriptional analysis.The transcriptome of dedifferentiated epithelial cells was subtracted from that of fully redifferentiated cells using complementary DNA representational difference analysis. In order to validate the results, gene overexpression in ciliated cells was confirmed by real-time PCR, and by comparing the present list of genes overexpressed in ciliated cells to lists obtained in previous studies.A total of 53 known and 12 unknown genes overexpressed in ciliated cells were identified. The majority (66%) of known genes had never previously been reported as being involved in ciliogenesis, and the unknown genes represent hypothetical novel transcript isoforms or new genes not yet reported in databases. Finally, several genes identified here were located in genomic regions involved in primary ciliary dyskinesia by linkage analysis.In conclusion, the present study revealed sequences of new cilia-related genes, new transcript isoforms and novel genes which should be further characterised to aid understanding of their function(s) and their probable disorder-related involvement.

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A novel ninein‐interaction protein, CGI‐99, blocks ninein phosphorylation by GSK3β and is highly expressed in brain tumors

Cited by 43 publications

References 32 publications

Ninein is released from the centrosome and moves bi-directionally along microtubules

Ninein is released from the centrosome and moves bi-directionally along microtubules

JAK2 Tyrosine Kinase Phosphorylates and Is Negatively Regulated by Centrosomal Protein Ninein

Identification of transcripts overexpressed during airway epithelium differentiation

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