p54nrb is a new regulator of progression of malignant melanoma.
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TLDR
It is demonstrated that p54(nrb) is strongly expressed and localized in the nucleus of both melanoma cell lines and melanoma tissue samples compared with normal human melanocytes or normal skin, respectively and, as a MIA target molecule, it seems to be involved in the development and progression of malignant melanoma.Abstract:
Nuclear RNA-binding protein p54(nrb) and its murine homolog NonO are known to be involved in a variety of nuclear processes including transcription and RNA processing. Melanoma inhibitory activity (MIA) has been shown to play an essential role in the progression of malignant melanoma and to influence melanoma-associated molecules and pathways in the early tumor formation steps. Interestingly, recent studies suggest that MIA is a regulator of p54(nrb). Here, we show that p54(nrb) is strongly expressed and localized in the nucleus of both melanoma cell lines and melanoma tissue samples compared with normal human melanocytes or normal skin, respectively. Furthermore, all tested melanoma cell lines revealed strong p54(nrb) promoter activity. Treatment with MIA-specific small interfering RNAs showed an influence of MIA on p54(nrb) expression on both messenger RNA (mRNA) and protein level. Knockdown of p54(nrb) protein in melanoma cell lines led to reduced proliferation rates and to a strong decrease in their migratory potential. In addition, attachment to laminin and poly-l-lysine was significantly increased. We could identify Connexin-43 (Cx-43) as a downstream target molecule of p54(nrb) as knockdown of p54(nrb) resulted in enhanced Cx-43 mRNA and protein levels. As a confirmation of these findings, melanoma cell lines showed very low Cx-43 expression levels compared with melanocytes. Our results demonstrate that p54(nrb) is highly expressed in malignant melanoma and, as a MIA target molecule, it seems to be involved in the development and progression of malignant melanoma.read more
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The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold
TL;DR: This work presents a coherent picture of DBHS proteins, integrating recent structural insights on dimerization, nucleic acid binding modalities and oligomerization propensity with biological function, and describes a family of dynamic proteins mediating a wide range of protein–protein and protein–nucleic acid interactions.
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PARP activation regulates the RNA-binding protein NONO in the DNA damage response to DNA double-strand breaks
Jana Krietsch,Marie-Christine Caron,Jean-Philippe Gagné,Chantal Ethier,Julien Vignard,Michel Vincent,Michèle Rouleau,Michael J. Hendzel,Guy G. Poirier,Jean-Yves Masson +9 more
TL;DR: The in vivo recruitment of NONO to DNA damage sites completely depends on PAR, generated by activated PARP-1 and it is shown that upon PAR-dependent recruitment, NONO stimulates nonhomologous end joining (NHEJ) and represses homologous recombination (HR) in vivo.
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Melanoma’s connections to the tumour microenvironment
TL;DR: The alterations in cell-cell communication in melanoma and the tumour microenvironment associated with melanoma development and progression are provided andnexins have been identified as key molecules for direct cell- cell communication.
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Immunologic and metabolic characteristics of HPV-negative and HPV-positive head and neck squamous cell carcinomas are strikingly different
Rosemarie Krupar,Katharina Robold,Doris Gaag,Gerrit Spanier,Marina Kreutz,Kathrin Renner,Claus Hellerbrand,Ferdinand Hofstaedter,Anja K. Bosserhoff +8 more
TL;DR: The results indicate that HPV-positive and HPV-negative carcinomas do not only differ in terms of tumor immune microenvironment, but also in Terms of tumor metabolism, characterized by an increased glucose and respiratory metabolism together with decreased lactate accumulation in HPV- positive HNSCC.
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SFPQ•NONO and XLF function separately and together to promote DNA double-strand break repair via canonical nonhomologous end joining.
TL;DR: These findings suggest that each protein has one or more unique activities, in addition to the DNA pairing revealed in vitro, that contribute to DNA repair in the more complex cellular milieu.
References
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Journal ArticleDOI
An Architectural role for a nuclear noncoding RNA : NEAT1 RNA is essential for the structure of paraspeckles
Christine Moulton Clemson,John N. Hutchinson,Sergio A. Sara,Alexander W. Ensminger,Alexander W. Ensminger,Archa H. Fox,Andrew Chess,Jeanne B. Lawrence +7 more
TL;DR: Results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain.
Journal ArticleDOI
Paraspeckles: a novel nuclear domain.
Archa H. Fox,Yun Wah Lam,Anthony K.L. Leung,Carol E. Lyon,Jens S. Andersen,Matthias Mann,Angus I. Lamond +6 more
TL;DR: It is shown that PSP1 accumulates in a new nucleoplasmic compartment, termed paraspeckles, that also contains at least two other protein components: PSP2 and p54/nrb.
Journal ArticleDOI
The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs.
Zuo Zhang,Gordon G. Carmichael +1 more
TL;DR: A Xenopus oocyte model system shows that a variety of hyperedited, inosine-containing RNAs are specifically retained in the nucleus, and provides evidence that one function of the complex identified here is to anchor hyperedite RNAs to the nuclear matrix, while allowing selectively edited mRNAs to be exported.
Journal ArticleDOI
Paraspeckles: nuclear bodies built on long noncoding RNA
Charles S. Bond,Archa H. Fox +1 more
TL;DR: Given the large numbers of long noncoding transcripts currently being discovered through whole transcriptome analysis, paraspeckles may be a paradigm for a class of subnuclear bodies formed around longnoncoding RNA.
Journal ArticleDOI
Purification and cDNA cloning of HeLa cell p54nrb, a nuclear protein with two RNA recognition motifs and extensive homology to human splicing factor PSF and Drosophila NONA/BJ6
TL;DR: The striking homology between p54nrb, PSF, and NONA/BJ6 defines a novel phylogenetically conserved protein segment, termed DBHS domain (for Drosophila behavior, human splicing), which may be involved in regulating diverse pathways at the level of pre-mRNA splicing.