Disease relevance of UBP1

• LBP-1 is a cellular protein which binds strongly to sequences around the human immunodeficiency virus type 1 (HIV-1) initiation site and weakly over the TATA box [1].
• In contrast, bacterial lactoferrin receptors have only been described for human pathogens in the family Neisseriaceae, and were believed to consist of a single protein, Lbp1, which is highly homologous to Tbp1 [2].
• Electrophoretic mobility shift assays with DNA sequences that encompass the LBP-1 binding site revealed increased levels of DNA-protein complex formation with nuclear extracts from HSV-1 infected as compared with uninfected U937 cells [3].
• Initial attempts at identifying the receptor proteins in Neisseria and Moraxella species using affinity isolation with immobilized lactoferrin under high stringency conditions presumptively identified a single 100 kDa receptor protein, LbpA (formerly Lbp1) [4].

High impact information on UBP1

• A cellular DNA binding protein, LBP-1, sequentially interacts in a concentration-dependent manner with two sites that surround the transcriptional initiation site of the human immunodeficiency virus type 1 (HIV-1) promoter [5].
• HeLa cell extracts were used to purify cellular proteins binding to portions of the enhancer region (EBP-1) and the TAR region (UBP-1) by a combination of conventional and DNA affinity chromatography [6].
• Purification of the human immunodeficiency virus type 1 enhancer and TAR binding proteins EBP-1 and UBP-1 [6].
• Potential binding sites for miR854 are absent from UBP1-like genes in fungi lacking the miRNA biogenetic machinery [7].
• As with UBP1, transient overexpression of UBA1a in protoplasts increases the steady-state levels of reporter mRNAs in a promoter-dependent manner [8].

Biological context of UBP1

• Comparison of the amino acid sequence of LBP-1 with entries in the available protein data bases revealed the identity of LBP-1c to alpha-CP2, an alpha-globin transcription factor [1].
• Severe mutations of the high affinity LBP-1 binding sites between -4 and +21 did not relieve the LBP-1-dependent block [9].
• In particular, YY1 and LBP-1 have been shown to cooperate in repressing HIV-1-long terminal repeat reporter gene expression by in vitro cotransfection experiments [10].
• Consistent with a role in pre-mRNA processing, overexpression of UBP1 in N. plumabaginifolia protoplasts enhances the splicing of suboptimal introns and increases the steady-state levels of reporter mRNAs, even intronless ones [8].
• Several studies have demonstrated that TAR DNA can bind cellular proteins, such as UBP-1/LBP-1, which repress HIV-1 gene expression and other factors which are involved in the generation of short, nonprocessive transcripts [11].

Anatomical context of UBP1

• Nicotiana plumbaginifolia UBP1 is an hnRNP-like protein associated with the poly(A)(+) RNA in the cell nucleus [8].
• The low-affinity site for LBP-1 (UBP-1) functioned as a negative regulator of LTR activity in undifferentiated macrophages, but this influence was lost upon differentiation [12].
• Transiently expressed LBP-1 proteins in COS-7 cells formed speckles in the nucleus [13].
• Investigation of subcellular localization of LBP-1 proteins fused to YFP revealed that the LBP-1b was localized in the nucleus, whereas LBP-1a and LBP-1c were exclusively localized in the cytosol [13].

Physical interactions of UBP1

• We have previously shown that LBP-1 represses HIV-1 transcription by inhibiting the binding of TFIID to the TATA box [1].
• The HSV-1-mediated induction correlates with the appearance of two NF-kappa B-specific proteins of 55 and 85 kDa in the nucleus and with the binding of 50-kDa nuclear protein to the LBP-1 binding site of the untranslated leader sequence of the HIV-1 long terminal repeat [14].

Other interactions of UBP1

• The cellular factor, LBP-1, can repress HIV-1 transcription by preventing the binding of TFIID to the promoter [9].
• However, addition of LBP-1 after RNA polymerase was stalled at +13 strongly inhibited further elongation ("chase") by reducing RNA polymerase processivity [9].
• Transcription factor NF2d9 (LBP-1a) interacts with the positive regulatory element for the xenobiotic responsive element [15].
• Moreover, we show that c-Myc can interact with the initiator binding proteins YY-1 and LBP-1 and can cooperate with these factors to synergistically repress HIV-1 LTR transcription [16].
• The maximum turnover number for LBP was approximately 150 molecules of LPS min-1 LBP-1 [17].

Analytical, diagnostic and therapeutic context of UBP1

• Gel-shift analysis shows that protein binds specifically to this region, but competition studies suggest that it is unlikely to be LBP-1 [18].
• Antiserum specific for either the M. catarrhalis Tbp1+2 molecules, the M. catarrhalis Lbp1 molecule, or for a commercial preparation of human lactoferrin did not react on western blots with the same organisms' affinity purified Lbp2 [2].

References