Disease relevance of NOLC1

• The sequence of Nopp140 contains several stretches of serine- and acidic amino acid-rich sequences which are also found in ICP4 of herpes simplex virus type 1, a known transcription factor that interacts with TFIIB [1].
• In summary, we demonstrate the existence of a novel Nopp140-mediated PKA signaling pathway that leads to the activation of agp, one of the major acute phase response genes [2].
• Identification of hNopp140 as a binding partner for doxorubicin with a phage display cloning method [3].
• In this paper, we report the cloning and overexpression of the soluble form of hNopp140 in Escherichia coli [4].

High impact information on NOLC1

• As a final link, we identified the coiled body-specific protein p80 coilin in a yeast two-hybrid screen with Nopp140 [5].
• Taken together, Nopp140 appeared to shuttle between the nucleolus and the coiled bodies, and to chaperone the transport of other molecules [5].
• The alternating positively and negatively charged repeat domain of Nopp140 was required for targeting to both organelles [5].
• They contain a subset of splicing snRNPs and several nucleolar antigens, including Nopp140 and fibrillarin [6].
• A previous study [Meier, U. T. & Blobel, G. (1992) Cell 70, 127-138] has shown that the nucleolar protein of rat liver cells (Nopp140) shuttles from the nucleolus to the nuclear envelope on distinct tracks [7].

Chemical compound and disease context of NOLC1

• Nopp140 is a mediator of the protein kinase A signaling pathway that activates the acute phase response alpha1-acid glycoprotein gene [2].

Biological context of NOLC1

• Human Nopp140, which interacts with RNA polymerase I: implications for rRNA gene transcription and nucleolar structural organization [8].
• Here we demonstrate that protein kinase A (PKA)-dependent phosphorylation of Nopp140, together with C/EBPbeta, induces agp gene expression synergistically [2].
• Furthermore, agp gene activation by the synergistic interaction of Nopp140 and C/EBPbeta is abolished by hnRNP K [9].
• Although p130 shows 74% identity to Nopp140, our observations suggest that during mitosis the functions of p130 are related to nucleologenesis [10].
• We identified a novel human nucleolar phosphoprotein p130 (130 kDa) using a strategy for selecting monoclonal antibodies against nuclear proteins which oscillate in the cell cycle. p130 is localized in interphase nucleoli in a dotted manner [10].

Anatomical context of NOLC1

• The nucleolar channel system exhibits an ultrastructure that is indistinguishable from R-rings, and nuclei of human endometrium harbor Nopp140 and ER marker containing structures [11].
• Intranuclear endoplasmic reticulum induced by Nopp140 mimics the nucleolar channel system of human endometrium [11].
• The superposition of (32)P-labelled ecto-nucleolar phosphoprotein p140 (ecto-Nopp140) with anti-Nopp140 immunostaining could be demonstrated in a wide range of cell lines without any exceptions, suggesting a nearly universal occurrence of cell-surface Nopp140 [12].
• The number of motor units in the gastrocnemius muscle was progressively reduced over time, down to 18% of the control value at P130 [13].

Associations of NOLC1 with chemical compounds

• These results suggested that doxorubicin might disrupt the cellular function of hNopp140 [3].
• One of the putative proteins, YKR412, is very rich in serine and has significant homology at the carboxyl end to Nopp140 phosphoprotein [14].

Physical interactions of NOLC1

• These results suggest that Nopp140 can interact with RNA polymerase I in vivo [8].

Co-localisations of NOLC1

• By double immunofluorescence, hNopp140 was colocalized with RNA polymerase I at the rDNA (rRNA genes) transcription active foci in the nucleolus [8].
• However, treacle fails to colocalize with Nopp140 to Cajal (coiled) bodies [15].

Regulatory relationships of NOLC1

• Ecto-protein kinase substrate p120 revealed as the cell-surface-expressed nucleolar phosphoprotein Nopp140: a candidate protein for extracellular Ca2+-sensing [12].

Other interactions of NOLC1

• In this study, we demonstrated that the largest subunit of RNA polymerase I, RPA194, was coimmunoprecipitated with the human Nopp140 (hNopp140) [8].
• Furthermore, maximal activation of the agp gene by PKA-phosphorylated Nopp140 depends on the presence of CREB and C/EBPbeta [2].
• The finding of LisH motifs in both treacle and Nopp140 reinforces previous observations of functional similarities between these nucleolar proteins [16].
• DAO-5 shows 33 % identity with human nucleolar phosphoprotein P130. dao-7 is similar to the mammalian ZFP36 protein [17].
• The best-studied representatives of this group are Nopp140 and nucleolin, proteins with structural and regulatory functions in rDNA transcription [18].

Analytical, diagnostic and therapeutic context of NOLC1

• Also, the effects of ATP and phosphorylation on the affinity of hNopp140 to doxorubicin are investigated by affinity dependent co-precipitation and surface plasmon resonance methods [19].

References