DNAJB1 stabilizes MDM2 and contributes to cancer cell proliferation in a p53-dependent manner

Qi, Min; Zhang, Jianglin; Zeng, Weiqi; Chen, Xiang

doi:10.1016/j.bbagrm.2013.12.003

Cited by 19 publications

(22 citation statements)

References 38 publications

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“…4). As reported earlier by Min Qi and colleagues, they found that HSP40/DNAJB1 inhibited cancer cell growth in vitro and in vivo by stabilizes MDM2 [21], which was consistent to our results although it worked though two different pathways.…”

Section: Discussionsupporting

confidence: 94%

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HSP40 Interacts with Pyruvate Kinase M2 and Regulates Glycolysis and Cell Proliferation in Tumor Cells

Huang

Zhang

et al. 2014

PLoS ONE

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Pyruvate kinase M2 (PKM2) is predominantly expressed in cancers, which is considered as a key regulator of the Warburg effect. In this study, HSP40 was identified as a novel binding partner of PKM2. HSP40-PKM2 association destabilized PKM2 protein through HSC70. In the presence of HSP40, PKM2 protein level and PKM2-mediated PDK1 expression were down-regulated. Moreover, HSP40 was involved in regulating glucose metabolism on PKM2 dependent way and at the mean time had an effect on mitochondrial oxygen respiration. In line with inhibition effect of HSP40 on glycolysis, the growth of cancer cells was inhibited by HSP40.Our data provided a new regulation mechanism of PKM2, which suggested a new therapeutic target for cancer therapy.

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Section: Discussionsupporting

confidence: 94%

“…PKM2 siRNA was generated with CATCTACCACTTGCAATTA oligonucleotide targeting exon 10 of the PKM2 transcript [9]. Three HSP40 siRNAs were used in our work, one HSP40 siRNA was designed by Genphama (1#) and the others were synthesized based on the published works (2# and 3#) [20], [21]:…”

Section: Methodsmentioning

confidence: 99%

HSP40 Interacts with Pyruvate Kinase M2 and Regulates Glycolysis and Cell Proliferation in Tumor Cells

Huang

Zhang

et al. 2014

PLoS ONE

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“…Specifically, as a protein implicated in stimulating the ATPase activity of Hsp70s, investigators showed that DNAJB1 inhibited p53-mediated apoptosis by destabilising PDCD5 in lung cancer 52. In contrast, Qi et al 53 found that it could decrease cell proliferation in a p53-dependent manner in breast cancers. Our data revealed that as an SE-associated oncogene, DNAJB1 was highly expressed in OSCC compared with other human cancers (see online supplementary figure S11), and it significantly promoted the growth and proliferation of OSCC cells.…”

Section: Discussionmentioning

confidence: 99%

Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma

Jiang

Lin

Mayakonda

et al. 2016

Gut

179

215

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Objectives Oesophageal squamous cell carcinoma (OSCC) is an aggressive malignancy and the major histological subtype of oesophageal cancer. Although recent large-scale genomic analysis has improved the description of the genetic abnormalities of OSCC, few targetable genomic lesions have been identified, and no molecular therapy is available. This study aims to identify druggable candidates in this tumour. Design High-throughput small-molecule inhibitor screening was performed to identify potent anti-OSCC compounds. Whole-transcriptome sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) were conducted to decipher the mechanisms of action of CDK7 inhibition in OSCC. A variety of in vitro and in vivo cellular assays were performed to determine the effects of candidate genes on OSCC malignant phenotypes. Results The unbiased high-throughput small-molecule inhibitor screening led us to discover a highly potent anti-OSCC compound, THZ1, a specific CDK7 inhibitor. RNA-Seq revealed that low-dose THZ1 treatment caused selective inhibition of a number of oncogenic transcripts. Notably, further characterisation of the genomic features of these THZ1-sensitive transcripts demonstrated that they were frequently associated with super-enhancer (SE). Moreover, SE analysis alone uncovered many OSCC lineage-specific master regulators. Finally, integrative analysis of both THZ1-sensitive and SE-associated transcripts identified a number of novel OSCC oncogenes, including PAK4, RUNX1, DNAJB1, SREBF2 and YAP1, with PAK4 being a potential druggable kinase. Conclusions Our integrative approaches led to a catalogue of SE-associated master regulators and oncogenic transcripts, which may significantly promote both the understanding of OSCC biology and the development of more innovative therapies.

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“…Of these genes, CCDC80, CLDN11, COL1A1, CTGF, DNAJB1, LGALS9, LTF, LUM, MT2A, MYH11, NMB, SOX4, and TIMP2 significantly expressed between the two age groups. DNAJB1 and SOX4 are expressed at low level in aged groups and it is reported that these genes contributes to p53 activity and promotes cellular apoptosis, respectively [44,45]. Similarly, TIMP2 that is expressed at low levels in aged groups inhibits angiogenesis [46,47].…”

Section: Discussionmentioning

confidence: 99%

Age-associated changes in bovine oocytes and granulosa cell complexes collected from early antral follicles

Itami

Kawahara-Miki

Kawana

et al. 2014

J Assist Reprod Genet

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DNAJB1 stabilizes MDM2 and contributes to cancer cell proliferation in a p53-dependent manner

Cited by 19 publications

References 38 publications

HSP40 Interacts with Pyruvate Kinase M2 and Regulates Glycolysis and Cell Proliferation in Tumor Cells

HSP40 Interacts with Pyruvate Kinase M2 and Regulates Glycolysis and Cell Proliferation in Tumor Cells

Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma

Age-associated changes in bovine oocytes and granulosa cell complexes collected from early antral follicles

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