HBP1: a HMG box transcriptional repressor that is targeted by the retinoblastoma family.

Tevosian, Sergei G.; Shih, Heather H.; Mendelson, Karen; Sheppard, Kelly-Ann; Paulson, K. Eric; Yee, Amy S.

doi:10.1101/gad.11.3.383

Cited by 147 publications

(261 citation statements)

References 67 publications

Supporting

Mentioning

243

Contrasting

Unclassified

Order By: Relevance

“…This was somewhat surprising given that p107 and p130 are more closely related to each other than to pRB (Mulligan and Jacks, 1998). Although di erential e ects of p107 and p130 on transcription have been previously noted (Wang et al, 1994;Tevosian et al, 1997), we could not discount the possibility that our results could simply re¯ect di erences in the levels of ectopically expressed pRB, p107, and p130 in AKR-2B ®broblasts. To address this issue, immunoblot analysis was used to compare the levels of each endogenous pocket protein with the corresponding over-expressed pocket protein in lysates from transfected cells.…”

Section: Expression Of Prb Is Necessary But Not Sufficient To Restorementioning

confidence: 60%

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

et al. 2000

View full text Add to dashboard Cite

Serum-stimulation of quiescent mouse ®broblasts results in transcriptional activation of tissue factor (TF), the cellular initiator of blood coagulation. This requires the rapid entry of c-Fos into speci®c AP-1 DNA-binding complexes and can be strongly inhibited by the adenovirus E1A 12S gene product. In this study, we utilized a panel of E1A mutants de®cient in cellular protein binding to analyse the molecular basis for E1A inhibition of a minimal, c-Fos-dependent TF promoter/ reporter construct in mouse AKR-2B ®broblasts. Mutations which impaired binding of the retinoblastoma tumor suppressor protein family members pRB, p107, and p130 relieved E1A-mediated inhibition of transcription in response to serum-stimulation or c-Fos overexpression. Inhibition was restricted to the G 0 to G 1 transition, consistent with the speci®city of E1A for hypophosphorylated forms of RB proteins. Although E1A mutants de®cient in CBP/p300 binding retained the ability to inhibit TF transcription, deletion of the aminoterminal portion of the CBP/p300 interaction domain was required to permit rescue of TF promoter activity by coexpression of pRB. Moreover, ectopic p107 could e ectively substitute for pRB in relieving E1A-mediated repression. In primary mouse embryo ®broblasts, activity of the minimal AP-1-dependent TF promoter was suppressed in Rb 7/7 cells compared to parallel Rb +/7 and Rb +/+ transfectants. Ectopic expression of either pRB or p107 markedly enhanced TF promoter activity in Rb 7/7 ®broblasts. Collectively, these data imply that pRB and p107 can cooperate with c-Fos to activate TF gene transcription in ®broblasts and suggest a requirement for another, as yet unidenti®ed, E1A-binding protein. Oncogene (2000) 19, 3352 ± 3362.

show abstract

Section: Expression Of Prb Is Necessary But Not Sufficient To Restorementioning

confidence: 60%

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Studies have shown that HBP1 has a key regulatory role in cell-cycle progression, cell-cycle exit, apoptosis and terminal differentiation in various tissues and cell types (Tevosian et al, 1997;Gartel et al, 1998;Shih et al, 1998;Lemercier et al, 2000), consistent with a role in tumor suppression. HBP1 gene targets include N-Myc, c-Myc, cyclin D1, myeloperoxidase, histone H1 and p47phox (Lin et al, 2001;Sampson et al, 2001;Berasi et al, 2004).…”

Section: Introductionmentioning

confidence: 69%

Macrophage migration inhibitory factor is a direct target of HBP1-mediated transcriptional repression that is overexpressed in prostate cancer

et al. 2010

View full text Add to dashboard Cite

Macrophage migration inhibitory factor (MIF) is a welldescribed proinflammatory mediator. MIF overexpression has been observed in many tumors and is implicated in oncogenic transformation and tumor progression. However, the molecular mechanisms responsible for regulating MIF expression remain poorly understood. In this study, we showed that the transcriptional repressor HBP1 (HMG box-containing protein 1) negatively regulates MIF expression. We first identified a large high-affinity HBP1 DNA-binding element at positions À811 to À792 from the transcriptional start site within the MIF promoter by computer analysis. Reporter analyses showed that this element was required for HBP1-mediated transcriptional repression. Furthermore, HBP1 associated with the MIF promoter in vivo and repressed endogenous MIF gene expression. Consistent with HBP1-mediated repression of MIF, low levels of HBP1 expression were associated with high levels of MIF expression in prostate cancer samples. Importantly, HBP1-mediated repression of MIF inhibited tumorigenic growth and invasion, and the repressive effect of HBP1 on tumorigenic growth and invasion could be partially rescued by the addition of recombinant MIF to the culture medium. Finally, prostate tumor samples with low HBP1 and high MIF expression were associated with a significant decrease in relapse-free survival. Taken together, these results indicated that HBP1 directly inhibited MIF gene transcription, and suggested that the loss of HBP1 expression or activity may contribute to the upregulation of MIF expression in prostate tumor tissue.

show abstract

“…We have previously isolated HBP1 as a retinoblastoma partner and have determined that it functions as a proliferation regulator by inhibiting oncogenic pathways as a transcriptional repressor (Lavender et al, 1997;Tevosian et al, 1997;Shih et al, 1998Shih et al, , 2001Lemercier et al, 2000;Smith et al, 2004). Recently, the HBP1 transcriptional repressor has been reported as a putative substrate for the p38 MAPK in cell-cycle arrest (Xiu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional factor HBP1 targets P16INK4A, upregulating its expression and consequently is involved in Ras-induced premature senescence

Wang

Liu

et al. 2010

Oncogene

Self Cite

View full text Add to dashboard Cite

Oncogene-mediated premature senescence has emerged as a potential tumor-suppressive mechanism in early cancer transitions. Many studies showed that Ras and p38 mitogen-activated protein kinase (MAPK) participate in premature senescence. Our previous work indicated that the HMG box-containing protein 1 (HBP1) transcription factor is involved in Ras-and p38 MAPK-induced premature senescence, but the mechanism of which has not yet been identified. Here, we showed that the p16 INK4A cyclin-dependent kinase inhibitor is a novel target of HBP1 participating in Ras-induced premature senescence. The promoter of the p16 INK4A gene contains an HBP1-binding site at position À426 to À433 bp from the transcriptional start site. HBP1 regulates the expression of the endogenous p16 INK4A gene through direct sequence-specific binding. With HBP1 expression and the subsequent increase of p16 INK4A gene expression, Ras induces premature senescence in primary cells. The data suggest a model in which Ras and p38 MAPK signaling engage HBP1 and p16 INK4A to trigger premature senescence. In addition, we report that HBP1 knockdown is also required for Ras-induced transformation. All the data indicate that the mechanism of HBP1-mediated transcriptional regulation is important for not only premature senescence but also tumorigenesis.

show abstract

HBP1: a HMG box transcriptional repressor that is targeted by the retinoblastoma family.

Cited by 147 publications

References 67 publications

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

Macrophage migration inhibitory factor is a direct target of HBP1-mediated transcriptional repression that is overexpressed in prostate cancer

Transcriptional factor HBP1 targets P16INK4A, upregulating its expression and consequently is involved in Ras-induced premature senescence

Contact Info

Product

Resources

About