Disease relevance of HNRPU

• Retrovirus integration site Mintb encoding the mouse homolog of hnRNP U [1].
• When tested in the human immunodeficiency virus type 1 transcription system, hnRNP U inhibits elongation rather than initiation of transcription by Pol II [2].
• With ascites fluids in isotonic buffer containing antibodies to nucleolar proteins p120 and C23, a maximum number of cells, 86 and 84%, respectively, were loaded following a 20-min incubation [3].
• Treatment with anti-lyn Abs coimmunoprecipitated, along with lyn product, the beta subunit of GM-CSFR and a phosphoprotein with a molecular mass of 120 kDa (p120) in the lysates of M-07e cells but not in the lysates of human monocyte-derived macrophages (HMDM) or human lymphoid leukemia cells [4].
• Using polyclonal anti-p120 antibody and anti-120 kDa nuclear ribonucleoprotein monoclonal antibody (mAb), p120 was identified as a nuclear ribonucleoprotein antigenically not related to EBV/C3dR [5].

High impact information on HNRPU

• The junctional proteins ZO-1 and p120 redistribute in a dotted circle peripheral to the brush border, in the absence of cell-cell contacts [6].
• By these criteria, the mammalian cells contain both GAP activities and the oocytes have only p120-like GAP activity [7].
• This protein occupies E3RS in a specific and stoichiometric manner, stabilizes the E3 component, and is likely responsible for its nuclear localization. hnRNP-U binding was abolished by competition with a pIkappaB(alpha) peptide, or by a specific point mutation in the E3RS WD region, indicating an E3-substrate-type interaction [8].
• Inhibition of HIV-1 gene expression by a fragment of hnRNP U [9].
• Whereas expression of Ki-67 or p120 on micrometastatic cells was observed only in 11 (15.9%) of 69 cancer patients analyzed, ErbB2+/CK18+ cells were found in 48 (67.6%) of 71 breast cancer patients and 14 (28.0%) of 50 patients with gastrointestinal cancer (P = .0001) [10].

Chemical compound and disease context of HNRPU

• Furthermore, p120 was tyrosine phosphorylated in avian cells expressing middle T antigen, the transforming protein of polyomavirus, as well as in rodent cells stimulated with either epidermal growth factor (EGF) or platelet-derived growth factor [11].
• Using the pre-S protein fused to glutathione S-transferase and immobilized on Sepharose beads, we have now identified an additional binding protein with a size of 120 kDa (p120). p120 expression is restricted to the liver, kidney, and pancreas, the three major organs of DHBV replication [12].
• Conserved serine-rich motifs identified in the repeat units of P120 and P140 were also found in the repeat units of the human granulocytotropic ehrlichiosis agent 130-kDa protein and of the fimbria-associated adhesin protein Fap1 of Streptococcus parasanguis [13].
• The glycoprotein genes of Ehrlichia chaffeensis (1,644 bp) and Ehrlichia canis (2,064 bp) encode proteins of 548 to 688 amino acids with predicted molecular masses of only 61 and 73 kDa but with electrophoretic mobilities of 120 kDa (P120) and 140 kDa (P140), respectively [13].
• Tyrosine phosphorylation of p120 in 1321N1 astrocytoma cells was less sensitive to modulation by peroxynitrite [14].

Biological context of HNRPU

• Here we show that GRIP120, one of the factors we have identified to interact with the glucocorticoid receptor, is identical to the heterogeneous nuclear ribonucleoprotein U (hnRNP U), a nuclear matrix protein binding to RNA as well as to scaffold attachment regions [15].
• Arginine methylation of scaffold attachment factor A by heterogeneous nuclear ribonucleoprotein particle-associated PRMT1 [16].
• Co-expression of hnRNP U attenuates the ability of YAP to increase the activity of a p73-driven Bax-luciferase reporter plasmid [17].
• Phosphorylation of pp100 and pp120 occurs in their extracellular domains at seryl residues of amino acid side chains [18].
• To gain insight into the mechanisms that govern this interference, we have now investigated the transcription of GR-dependent reporter genes in Ltk(-) cells transiently transfected with a variety of hnRNP U constructs [19].

Anatomical context of HNRPU

• Binding of PRMT1 occurs through physical interaction with scaffold attachment factor A (SAF-A), also known as hnRNP-U, which is quantitatively methylated by PRMT1 in all investigated cell lines as determined by a novel, highly specific, methylation-sensitive antibody [16].
• The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U [15].
• We have chosen HeLa cells as a source for the biochemical characterization and isolation of pp100 and pp120 [18].
• Thus, pp120 may serve as a link between Syk and PLC gamma 1, coupling the B-cell antigen receptor to the phosphatidylinositol pathway [20].
• Immunofluorescence and immunohistochemistry using differentiation, proliferation, and adhesion markers showed that DGC initiation seems to occur at the proliferative zone (the upper neck) of the gastric epithelium and correlates with absent or reduced expression of junctional proteins (beta-actin, p120, Lin-7) [21].

Associations of HNRPU with chemical compounds

• Using a nuclear transport-deficient deletion of hnRNP U, nuclear translocation was seen to be dependent on GR and dexamethasone [15].
• Crosslinking of cell surface IgM led to rapid activation of both tyrosine and serine/threonine protein kinase activities that resulted in phosphorylation in vitro of proteins coprecipitating with Syk--in particular, a serine/threonine phosphorylated protein 120 kDa in size (pp120) [20].
• We have investigated its signal transduction mechanism by using the human pre-B cell line Nalm-6, and have found that it stimulates tyrosine phosphorylation of various proteins: pp27, pp43, pp54, pp64, pp78, pp90, pp105, and pp120 [22].
• Induction of p120 by actinomycin-D occurred at concentrations which inhibit RNA synthesis and p120 mRNA levels [23].
• On sucrose density gradients, p120 from HeLa cells sedimented in the 60-80S region, in which preribosomal particles sedimented using similar extraction and centrifugation procedures [24].

Physical interactions of HNRPU

• The E1B-AP5 gene encodes a novel nuclear RNA-binding protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) family that is highly related to hnRNP-U/SAF-A [25].
• We showed that hnRNP U can bind TFIIH in vivo under certain conditions and inhibit TFIIH-mediated CTD phosphorylation in vitro [2].
• The necdin-binding site of hnRNP U was located near a carboxyl-terminal region that mediated the association between hnRNP U and the nuclear matrix [26].

Regulatory relationships of HNRPU

• In contrast, hnRNP U has no effect when co-expressed with a truncated YAP protein lacking the hnRNP U-binding site [17].
• The abilities of hnRNP U to inhibit TFIIH-mediated CTD phosphorylation and its Pol II association are necessary for hnRNP U to mediate the repression of Pol II elongation [2].
• These results suggest that necdin suppresses cell proliferation through its interaction with hnRNP U in the specific subnuclear structure [26].
• Ecto-protein kinase substrate p120 revealed as the cell-surface-expressed nucleolar phosphoprotein Nopp140: a candidate protein for extracellular Ca2+-sensing [27].

Other interactions of HNRPU

• Furthermore, hnRNP U and YAP only interact in the nucleus, suggesting that the association between the two proteins is regulated [17].
• Actin and hnRNP U cooperate for productive transcription by RNA polymerase II [28].
• The structure revealed a unique four-helix bundle with a topology of an up-down-extended loop-down-up, a part of which the helix-extended loop-helix represented the SAP (SAF-A/B, Acinus, and PIAS) motif [29].
• Like p53, induction of p120 by anticancer drugs did not require transcription [23].
• The 120-kDa serine/threonine phosphorylated protein that coprecipitated with PLC gamma 1 resembled the Syk-associated pp120 by several criteria [20].

Analytical, diagnostic and therapeutic context of HNRPU

• The subnuclear distribution of GR and hnRNP U was characterized by indirect immunofluorescent labeling and confocal laser microscopy demonstrating a colocalization of both proteins [15].
• Two major 32P-labeled proteins, designated as pp100 and pp120 after their apparent molecular masses on SDS-PAGE under reducing and nonreducing conditions, have repeatedly appeared in the phosphoprotein spectra of different cell types [18].
• Using chromatin immunoprecipitations, we established that both p300 and SAF-A bind to S/MAR elements in the transiently silent topoisomerase I gene prior to its activation at G(1) during cell cycle [30].
• Using affinity chromatography on fractionated HeLa cells, we found that hnRNP U binds actin through a short amino acid sequence in its C-terminal domain [28].
• Post-transcriptional gene silencing of hnRNP U and nuclear microinjections of a short peptide encompassing the hnRNP U actin-binding sequence inhibited BrUTP incorporation in vivo [28].

References