The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A

Lavender, Paul; Vandel, Laurence; Bannister, Andrew J.; Kouzarides, Tony

doi:10.1038/sj.onc.1201243

Cited by 64 publications

(78 citation statements)

References 25 publications

(31 reference statements)

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“…Only few studies have reported that HBP1 is a transcriptional activator in myeloid differentiation and transformation (Lavender et al, 1997;Yao et al, 2005). Actually, HBP1 has dual function in transcription.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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

Wang

Liu

et al. 2010

Oncogene

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…In addition to the HMG box-like sequence, which is the DNA-binding region, HBP1 contains two pocket protein-binding sequences: an LXCXE site and an IXCXE site. Human HBP1 also contains a 28 amino-acid sequence that shows 86% homology with a transcriptional activation domain previously identified in rat HBP1 (Lavender et al, 1997); the activation domain is flanked by two putative repressor domains. The presence of these sequences suggests that human HBP1 may activate and/or repress the transcription of other genes (Sampson et al, 2001).…”

Section: Introductionmentioning

confidence: 90%

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

et al. 2010

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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.

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“…Bacterial expression plasmids are: pGEX (Pharmacia), pQE30 (Qiagen expression systems). For the mammalian expression construct, an HA epitope (a peptide derived from influenza hemagglutinin protein)-tagged expression vector pCMV 5Ј2N3T (Lavender et al 1997) was used. Sequencing of PCR fragments, point mutations, and cDNA inserts from positive clones of the two-hybrid screen was performed with an automatic sequencer by the dideoxy termination method.…”

Section: Methodsmentioning

confidence: 99%

DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D

Yavuzer¹,

Smith²,

Bliss³

et al. 1998

Genes Dev.

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DNA-dependent protein kinase (DNA-PK), which is involved in DNA double-strand break repair and V(D)J recombination, is comprised of a DNA-targeting component termed Ku and an ∼465-kD catalytic subunit, DNA-PK cs . Although DNA-PK phosphorylates proteins in the presence of DSBs or other discontinuities in the DNA double helix in vitro, the possibility exists that it is also activated in other circumstances via its association with additional proteins. Here, through use of the yeast two-hybrid screen, we discover that the recently identified high affinity DNA binding protein C1D interacts with the putative leucine zipper region of DNA-PK cs . Furthermore, we show that C1D can interact with DNA-PK in mammalian cells and that C1D is a very effective DNA-PK substrate in vitro. Finally, we establish that C1D directs the activation of DNA-PK in a manner that does not require DNA termini. Therefore, these studies provide a function for C1D and suggest novel mechanisms for DNA-PK activation in vivo.

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The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A

Cited by 64 publications

References 25 publications

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

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

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

DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D

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