Disease relevance of HBP1

• As an initial step toward clinical relevance, a bioinformatics approach shows that the relative expression levels of HBP1 and WIP1 correlated with decreased relapse-free survival in breast cancer patients [1].
• In cell lines, we had previously isolated HBP1 as a retinoblastoma (RB) target but have determined that it functions as a proliferation regulator by inhibiting oncogenic pathways as a transcriptional repressor [1].
• Directed enzyme evolution of 2-hydroxybiphenyl 3-monooxygenase (HbpA; EC ) from Pseudomonas azelaica HBP1 resulted in an enzyme variant (HbpA(ind)) that hydroxylates indole and indole derivatives such as hydroxyindoles and 5-bromoindole [2].
• Gel mobility shift and DNase I footprint analyses showed that this protein interacts with homologous sequences in the regulatory regions for the transcription of the cauliflower mosaic virus (CaMV) 35S RNA and nopaline synthase (NOS) genes, evidence that HBP-1 may bind to hexameric sequences in the regulatory regions of various genes [3].
• Ectopic activation of lymphoid high mobility group-box transcription factor TCF-1 and overexpression in colorectal cancer cells [4].

High impact information on HBP1

• The deduced amino acid sequence indicates that HBP-1 contains the leucine zipper motif, which represents a characteristic property of several eukaryotic transcription factors [5].
• Fifth, the expression of HBP1 lead to efficient cell cycle arrest [6].
• The arrest phenotype was manifested in the presence of optimal proliferation signals, suggesting that HBP1 exerted a dominant regulatory role [6].
• Here, we show that HBP1 is a repressor of the cyclin D1 gene and inhibits the Wnt signaling pathway [7].
• Mice transgenic for a hCD2 LCR construct carrying a deletion of the HBP1-binding sequences show a propensity for PEV if the transgene integrates in a heterochromatic region of the chromosome such as the centromere or telomere [8].

Chemical compound and disease context of HBP1

• Suppression of Wnt Signaling by the Green Tea Compound (-)-Epigallocatechin 3-Gallate (EGCG) in Invasive Breast Cancer Cells: REQUIREMENT OF THE TRANSCRIPTIONAL REPRESSOR HBP1 [9].

Biological context of HBP1

• We therefore propose that HBP1 mediates a link between the cell cycle control machinery and cell differentiation signals [10].
• With HBP1 expression and the subsequent reduction in p47phox gene expression, intracellular superoxide production was correspondingly reduced [11].
• Through modulating the expression of specific chromatin-associated proteins such as histone H1(0), HBP1 plays a vital role in chromatin remodeling events during the arrest of cell proliferation in differentiating cells [10].
• Two specific proteins, ZNF191, a zinc finger protein, and HBP1, an HMG box transcription factor, which bind the TCAT motif, were then cloned [12].
• The amino acid sequence specified by the coding region shows 95% homology with the rat HBP1 protein [13].

Anatomical context of HBP1

• Human HBP1 appears to be a novel transcription factor which is likely to play an important role in regulating transcription in developing myeloid cells [13].
• We have expressed human HBP1 protein both in vitro and in prokaryotic and eukaryotic cells [13].
• We prepared transient and stable transfectants of the myeloblast cell line K562, which overexpress HBP1 mRNA and protein [14].
• HBP1 overexpression enhanced differentiation of K562 cells towards erythroid and megakaryocyte lineages, as evidenced by increased hemoglobin and CD41a expression [14].
• Using transgenic mice in which HBP1 expression was specifically increased in hepatocytes under control of the transthyretin promoter, we determined the impact of HBP1 on synchronous cell cycle reentry following partial hepatectomy [15].

Physical interactions of HBP1

• The HMG box containing protein UBF binds to the promoter of vertebrate ribosomal repeats and is required for their transcription by RNA polymerase I in vitro [16].

Regulatory relationships of HBP1

• Furthermore, HBP1 repressed the expression of the endogenous p47phox gene through sequence-specific binding [11].
• In transient co-transfection experiments HBP1 enhances MPO promoter activity [13].
• Both E2Fs and HBP1 regulate p21 transcription through cis-acting elements located between nucleotides -119 to +16 of the p21 promoter and the DNA binding domains of each of these proteins are required for activity [17].

Other interactions of HBP1

• The promoter of the p47phox gene contains six tandem high-affinity HBP1 DNA-binding elements at positions -1243 to -1318 bp from the transcriptional start site which were required for repression [11].
• We show that HBP1 can interact with one of these, RB, both in vitro and in mammalian cells [18].
• Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene [11].
• The opposing effects of E2Fs and HBP1 on p21 promoter activity suggest that interplay between these factors may determine the level of p21 transcription in vivo [17].
• Fas ligand mRNA levels were increased in HBP1 transfectants, suggesting involvement of the Fas/Fas ligand pathway [14].

Analytical, diagnostic and therapeutic context of HBP1

• In contrast, the onset of the immediate-early response following partial hepatectomy was unchanged in HBP1 transgenic mice [15].
• Our subsequent work demonstrated that HBP1 coordinates differentiation in cell culture models [15].

References