A Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase (MEK)-dependent Transcriptional Program Controls Activation of the Early Growth Response 1 (EGR1) Gene during Amino Acid Limitation

Shan, Jixiu; Balasubramanian, M.; Donelan, William; Fu, Lingchen; Hayner, Jaclyn N.; Lopez, Maria-Cecilia; Baker, Henry V.; Kilberg, Michael S.

doi:10.1074/jbc.m114.565028

Cited by 28 publications

(36 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed that ATF4/CHOP-independent genes involved in activation of the AAR pathway (33,34) were induced by VGCC/K Ca block ( Fig. 3E; Table 2).…”

Section: Reactome Analysis Identifies Induction Of Aar In Addition Tomentioning

confidence: 54%

Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses

et al. 2017

View full text Add to dashboard Cite

Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca and K channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstream signaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na, which compromised Na-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas. .

show abstract

“…We also observed that ATF4/CHOP-independent genes involved in activation of the AAR pathway (33,34) were induced by VGCC/K Ca block ( Fig. 3E; Table 2).…”

Section: Reactome Analysis Identifies Induction Of Aar In Addition Tomentioning

confidence: 54%

Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses

et al. 2017

View full text Add to dashboard Cite

show abstract

“…It is a controversial topic on the roles of Egr-1 in HCC. Hao and his colleagues reported that Egr-1 expression was down-regulated in hepatocellular carcinoma, and re-expression of Egr-1 decreased cell growth and tumorigenicity in nude mice [42]. Conversely, Tian et.…”

Section: Discussionmentioning

confidence: 94%

Egr-1 promotes hypoxia-induced autophagy to enhance chemo-resistance of hepatocellular carcinoma cells

Peng

Xiong

et al. 2016

Experimental Cell Research

View full text Add to dashboard Cite

“…8C ) does not perfectly mimic EGR1 induction by serum, but it is similar at the pre-mRNA level. Because EGR1 induction is likely at the level of RNA synthesis [ 64 , 65 , 89 , 90 ], it remains possible that ORF57 is initiating this transcriptional response. If ORF57 induces EGR1, it is not fully induced as there is still an ~10-fold induction of EGR1 mRNA in the presence of ORF57 (compare mRNA levels at 0 with 30 min, Fig.…”

Section: Discussionmentioning

confidence: 99%

HITS-CLIP Analysis Uncovers a Link between the Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein and Host Pre-mRNA Metabolism

et al. 2015

View full text Add to dashboard Cite

The Kaposi’s sarcoma associated herpesvirus (KSHV) is an oncogenic virus that causes Kaposi’s sarcoma, primary effusion lymphoma (PEL), and some forms of multicentric Castleman’s disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP). As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5´ ends. The position of these 5´-bound fragments correlated closely with the 5´-most exon-intron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9) and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation.

show abstract

A Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase (MEK)-dependent Transcriptional Program Controls Activation of the Early Growth Response 1 (EGR1) Gene during Amino Acid Limitation

Cited by 28 publications

References 50 publications

Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses

Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses

Egr-1 promotes hypoxia-induced autophagy to enhance chemo-resistance of hepatocellular carcinoma cells

HITS-CLIP Analysis Uncovers a Link between the Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein and Host Pre-mRNA Metabolism

Contact Info

Product

Resources

About