Role of p73 in Regulating Human Caspase-1 Gene Transcription Induced by Interferon-γ and Cisplatin

Jain, Nishant; Gupta, Sanjeev; Sudhakar, Cherukuri; Radha, Vegesna; Swarup, Ghanshyam

doi:10.1074/jbc.m413261200

Cited by 24 publications

(45 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The association of the overexpression of DTAp73 isoforms with shorter survival could be due to some putative TP73 target genes being involved in drug resistance, invasiveness, and other stages of the tumorigenesis process. ABCB1, HMGB1, and CASP1, among others, have been described as TP73 targets (35)(36)(37)(38). These previous data are supported by the fact that the ectopic expression of DNp73 in our cellular system induces the upregulation of ABCB1 and HMGB1.…”

Section: Discussionsupporting

confidence: 85%

“…In addition, TP73 regulates the expression of genes associated with drug resistance. Specifically, upregulation of the activity of ABCB1, HMGB1, and CASP1 promoters by p73 variants has been described previously (35)(36)(37)(38). MDR1 is a P-glycoprotein that acts as an energydependent drug-efflux pump and is often overexpressed in multidrug-resistant tumor cells (39).…”

Section: Introductionmentioning

confidence: 95%

“…HMGB1 is involved in several biologic processes, including invasiveness, transcription, DNA repair, and drug resistance mechanisms (40,41). Lastly, CASP-1 plays an important role in several apoptosis pathways (38) and has been described as being downregulated in several tumor types (42,43). In addition, overexpression of ABCB1 and HMGB1 has been associated with poor prognosis of cancer patients (44)(45)(46).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic Impact of ΔTAp73 Isoform Levels and Their Target Genes in Colon Cancer Patients

Soldevilla

Díaz

Silva

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Cumulative data support the role of DTAp73 variants in tumorigenic processes such as drug resistance. We evaluate the impact of TP73 isoforms and their putative target genes ABCB1, HMGB1, and CASP1 on the survival of colon cancer patients and the correlation between their expressions.Experimental Design: We determined in 77 colon cancer patients the expression of DEx2p73, DEx2/ 3p73, DNp73, TAp73, ABCB1, HMGB1, and CASP1 by quantitative real-time reverse transcriptase-PCR. Tumor characteristics, disease-free survival, and overall survival (OS) were examined in each patient. Functional experiments were carried out to check whether ectopic expression of DNp73 modifies the proliferation, drug resistance, migration, and invasion properties of colon tumor cells and the expression of ABCB1, HMGB1, and CASP1.Results: Positive correlations were observed between the expression levels of DTAp73 variants and HMGB1. Furthermore, a trend was observed for ABCB1. Overexpression of DEx2/3p73 and DNp73 isoforms was significantly associated with advanced stages (P ¼ 0.04 and P ¼ 0.03, respectively) and predicted shortened OS (P ¼ 0.04 and P ¼ 0.05, respectively). High levels of ABCB1 and HMGB1 were associated with shorter OS (P ¼ 0.04 and P ¼ 0.05, respectively). Multivariate analysis showed that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS (P ¼ 0.008). Ectopic expression of DNp73 was associated with an increase in proliferation and drug resistance.Conclusions: The positive correlation between DTAp73 variants and HMGB1 and ABCB1 expression supports them as TP73 targets. The fact that upregulation of DTAp73 isoforms was associated with shortened OS, increase in proliferation, and drug resistance confirms their oncogenic role and plausible value as prognostic markers. ABCB1 and HMGB1, putative DTAp73 target genes, strongly predict OS in an independent manner, making clear the importance of studying downstream TP73 targets that could predict the outcome of colon cancer patients better than DTAp73 variants themselves do.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic Impact of ΔTAp73 Isoform Levels and Their Target Genes in Colon Cancer Patients

Soldevilla

Díaz

Silva

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Cells grown on coverslips or dishes were infected with adenoviruses and processed after 72 hours for efficient knockdown. The shRNA expression vector targeting human TBC1D17 was made using a plasmid vector with a U6 promoter as described previously (Jain et al, 2005;Yu et al, 2002). The TBC1D17 sequence targeted by shRNA was from nucleotides 69 to 87 of the coding region (GenBank accession no.…”

Section: Knockdown Of Optineurin and Tbc1d17mentioning

confidence: 99%

“…The immunoprecipitated proteins were washed three times with wash buffer [20 mM HEPES pH 7.4, 0.1% Triton X-100, 150 mM NaCl, 10% (v/v) glycerol, 1 mM PMSF and protease inhibitors], eluted by boiling in SDS sample buffer and resolved in by SDS-PAGE (8-12% gels). The proteins were transferred onto nitrocellulose membrane for western blot analysis as described previously (Jain et al, 2005).…”

Section: Knockdown Of Optineurin and Tbc1d17mentioning

confidence: 99%

Optineurin mediates negative regulation of Rab8 function by TBC1D17, a GTPase activating protein

Vaibhava

Nagabhushana

Chalasani

et al. 2012

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

SummaryRab GTPases regulate various membrane trafficking pathways but the mechanisms by which GTPase-activating proteins recognise specific Rabs are not clear. Rab8 is involved in controlling several trafficking processes, including the trafficking of transferrin receptor from the early endosome to the recycling endosome. Here, we provide evidence to show that TBC1D17, a Rab GTPase-activating protein, through its catalytic activity, regulates Rab8-mediated endocytic trafficking of transferrin receptor. Optineurin, a Rab8-binding effector protein, mediates the interaction and colocalisation of TBC1D17 with Rab8. A non-catalytic region of TBC1D17 is required for direct interaction with optineurin. Co-expression of Rab8, but not other Rabs tested, rescues the inhibition of transferrin receptor trafficking by TBC1D17. The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment. Through its catalytic activity, TBC1D17 inhibits recruitment of Rab8 to the tubules and reduces colocalisation of transferrin receptor and Rab8. Knockdown of optineurin or TBC1D17 results in enhanced recruitment of Rab8 to the tubules. A glaucoma-associated mutant of optineurin, E50K, causes enhanced inhibition of Rab8 by TBC1D17, resulting in defective endocytic recycling of transferrin receptor. Our results show that TBC1D17, through its interaction with optineurin, regulates Rab8-mediated endocytic recycling of transferrin receptor and recruitment of Rab8 to the endocytic recycling tubules. We describe a mechanism of regulating a Rab GTPase by an effector protein (optineurin) that acts as an adaptor to bring together a Rab (Rab8) and its GTPase-activating protein (TBC1D17).

show abstract

Abundance of d‐2‐hydroxyglutarate in G2/M is determined by FOXM1 in mutant IDH1‐expressing cells

et al. 2019

Self Cite

View full text Add to dashboard Cite

Isocitrate dehydrogenases (IDHs) are metabolic enzymes that are mutated in several cancers, resulting in overproduction of d‐2‐hydroxyglutarate (D‐2HG). However, the signalling pathways and factors that regulate mutant IDHs or their metabolites remain elusive. Here, we report that in synchronized cells and cells treated with anti‐mitotic agents, wild‐type and mutant IDH proteins are induced maximally in G2/M. Moreover, mutant IDH1‐expressing cells arrested in G2/M harbour high D2HG levels. Genetic or pharmacological perturbation of Forkhead box protein M1 (FOXM1) abrogates the levels of IDH1 mRNA, protein and D2HG in G2/M. Conversely, overexpression of FOXM1 or hyperactive FOXM1 activates the IDH1 promoter and increases the abundance of its protein levels. In summary, our results show that in G2/M, higher D2HG levels are dependent on FOXM1‐mediated transcription of IDH1.

show abstract

Role of p73 in Regulating Human Caspase-1 Gene Transcription Induced by Interferon-γ and Cisplatin

Cited by 24 publications

References 44 publications

Prognostic Impact of ΔTAp73 Isoform Levels and Their Target Genes in Colon Cancer Patients

Prognostic Impact of ΔTAp73 Isoform Levels and Their Target Genes in Colon Cancer Patients

Optineurin mediates negative regulation of Rab8 function by TBC1D17, a GTPase activating protein

Abundance of d‐2‐hydroxyglutarate in G2/M is determined by FOXM1 in mutant IDH1‐expressing cells

Contact Info

Product

Resources

About