Transcription factors Oct-1 and NF-YA regulate the p53-independent induction of the GADD45 following DNA damage

Jin, Shunqian; Fan, Feiyue; Fan, Wenhong; Zhao, Hongcheng; Tong, Tong; Blanck, Patricia; Alomo, Isaac; Baskaran, Rathinasamy; Zhan, Qimin

doi:10.1038/sj.onc.1204390

Cited by 94 publications

(98 citation statements)

References 35 publications

(40 reference statements)

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“…NF-Y activation of BRLF1 may be mediated by the physical interaction of NF-Y with one or a combination of the three consensus sequences within the distal promoter region. Alternatively, this interaction might also be occurring through participation of cofactors, such as Oct-1 (15) or Sp1 (39). Finally, NF-Y may also be exerting its effect indirectly through the up-regulation of the transcription factor Sp3 and its subsequent involvement in BRLF1 autoactivation (49), allowing for a positive feedback loop with further amplification of NF-Y -mediated lytic gene expression (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…NF-Y is an important transcription factor that has been implicated as a critical regulator of genes in multiple biological processes, including parathyroid hormone activation (13) and multidrug resistance 1 expression (14). More recently, NF-Y has been shown to be important in the regulation of other genes involved in cellular stress response, such as GADD45 and HSP (15,16). This current work characterizes the latent to lytic activation of EBV in response to clinically relevant stress agents in NPC, shown by an increase in BRLF1 and BZLF1 expression, mediated in part by NF-Y.…”

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confidence: 99%

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Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer

Chia

Leung

Krushel

et al. 2008

Clinical Cancer Research

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Purpose: The Epstein Barr virus (EBV) is intimately associated with nasopharyngeal cancer (NPC) in a latent state expressing a limited number of genes.The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model. Experimental Design: C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 Ag/mL) assayed subsequently for relative EBV copy number (BamHI) and lytic gene expression (BRLF1 and BZLF1) using quantitative real-time PCR. Chromatin immunoprecipitation was conducted to assess the interaction of the transcription factor nuclear factor-Y (NF-Y) with promoter sequences. Results: Radiation-induced and cisplatin-induced BamHI expression, along with increased levels of BRLF1 and BZLF1 in a dose-dependent and time-dependent manner, associated with the immediate nuclear transactivation of the transcription factor NF-Y and its own increased transcription of NF-Y subunits 8 h posttreatment. In silico analysis revealed three putative NF-Y consensus-binding sequences in the promoter region of BRLF1, which all interacted with NF-Y in response to radiation and cisplatin, confirmed using chromatin immunoprecipitation. Introduction of dominant-negative NF-YA reduced BRLF1 expression after radiation and cisplatin by 2.8-fold; in turn, overexpression of NF-YA resulted in a 2-fold increase in both BRLF1 and BZLF1 expression. Conclusions: These results show that NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state. This novel insight could provide a potential therapeutic strategy to enhance NPC response to radiation and cisplatin.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer

Chia

Leung

Krushel

et al. 2008

Clinical Cancer Research

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“…Yet, similar effects on Oct-1 have also been implicated in the cellular response to other types of DNA damage, such as ultraviolet, cisplatin and methylmethane sulfonate, which do not lead to the activation of DNA-PK (Zhao et al, 2000a). Recent work has indicated that Oct-1 is involved in the transcriptional regulation of ultraviolet-induced genes (Jin et al, 2001;Takahashi et al, 2001;Luo et al, 2003) and we have shown that Oct-1 deficiency results in increased sensitivity to several DNA-damaging agents (Tantin et al, 2005). Thus, it will be interesting to determine the extent to which the 13 S/T residues identified in this study play a role in the response of Oct-1 to other DNA-damaging agents.…”

Section: Discussionmentioning

confidence: 68%

“…Somewhat paradoxically, we have determined that Oct-1 protein levels increase subsequent to ionizing radiation (IR) exposure, whereas at the same time H2B and U2 expression is down-regulated (Zhao et al, 2000a;Jin et al, 2001;Schild-Poulter et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

DNA-PK phosphorylation sites on Oct-1 promote cell survival following DNA damage

et al. 2007

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“…These observations suggest that GADD45g can be considered as a functional tumor suppressor gene. Although several studies have addressed the transcriptional regulation of the GADD45a and b genes (Zhan et al, 1994;Constance et al, 1996;Marhin et al, 1997;De Smaele et al, 2001;Jin et al, 2001;Takahashi et al, 2001), very little is known about the regulation of the GADD45g gene. In fact, to the best of our knowledge, there is only a single study addressing GADD45g gene regulation where it was suggested that transcription factors C/EBPb and d might be involved in GADD45g promoter activation during differentiation of M1 cells (Jung et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The histone deacetylase inhibitor trichostatin A induces GADD45γ expression via Oct and NF-Y binding sites

2007

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The GADD45c protein is a potential tumor suppressor whose expression is reduced in several tumors. However, very little is known about the regulation of its expression. We have determined that the most relevant region of its promoter lies between nucleotides À112 and À54, relative to the transcription start site. Putative Oct and NF-Y elements were found in this region and factors belonging to these families interacted with these elements in vitro and with the promoter in vivo. Mutation of these elements reduced the basal activity of the promoter, suggesting that both sites are essential for basal expression. These factors interact with chromatin modifying proteins and we found that histone deacetylase 1 or silencing mediator for retinoid and thyroid hormone receptor overexpression reduced the basal activity of the promoter. In contrast, forced expression of the histone acetylase protein PCAF or cell treatment with the HDAC inhibitor trichostatin A increased GADD45c mRNA levels and induced GADD45c promoter activity through its Oct and NF-Y elements. Moreover, ectopic expression of a dominantnegative version of NF-YA strongly inhibited trichostatin A-induced activation of the promoter. Our data strongly suggest that inhibition of deacetylase activity could potentially be used for treatment of tumors where GADD45c expression is reduced.

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Transcription factors Oct-1 and NF-YA regulate the p53-independent induction of the GADD45 following DNA damage

Cited by 94 publications

References 35 publications

Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer

Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer

DNA-PK phosphorylation sites on Oct-1 promote cell survival following DNA damage

The histone deacetylase inhibitor trichostatin A induces GADD45γ expression via Oct and NF-Y binding sites

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