Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury

Ho, Jin‐Nyoung; Wee, Hee Jun; Seo, Ji Hae; Ahn, Bum Ju; Park, Ji‐Hyeon; Yang, Jun Mo; Lee, Sae Won; Lee, Ok Hee; Hj, Lee; Gelman, Irwin H.; Arai, Ken; Lo, Eng H.; Kim, Kyu Won

doi:10.1038/ncomms5952

Cited by 28 publications

(21 citation statements)

References 64 publications

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“…For some of these, EMT-related functions have not yet been found in breast cancer; for example, MFI2 has only been shown to mediate the EMT in melanoma, so further exploration of their roles in the EMT and chemoresistance in breast cancer is worthwhile. The expression of three genes, AKAP12 47 , DKK3 48 , and TUSC3 49 , in chemoresistant MCF-7 cells and TNBC samples was not consistent with previous reports. This may be due to differences in the types of cells used, so whether they play different roles in chemoresistant TNBC cells needs further study.…”

Section: Discussioncontrasting

confidence: 79%

Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer

Gao

et al. 2016

Sci Rep

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Cancer chemoresistance is regulated by complex genetic and epigenetic networks. In this study, the features of gene expression, methylation, and microRNA (miRNA) expression were investigated with high-throughput sequencing in human breast cancer MCF-7 cells resistant to adriamycin (MCF-7/ADM) and paclitaxel (MCF-7/PTX). We found that: ① both of the chemoresistant cell lines had similar, massive changes in gene expression, methylation, and miRNA expression versus chemosensitive controls. ② Pairwise integration of the data highlighted sets of genes that were regulated by either methylation or miRNAs, and sets of miRNAs whose expression was controlled by DNA methylation in chemoresistant cells. ③ By combining the three sets of high-throughput data, we obtained a list of genes whose expression was regulated by both methylation and miRNAs in chemoresistant cells; ④ Expression of these genes was then validated in clinical breast cancer samples to generate a 17-gene signature that showed good predictive and prognostic power in triple-negative breast cancer patients receiving anthracycline-taxane-based neoadjuvant chemotherapy. In conclusion, our results have generated a new workflow for the integrated analysis of the effects of miRNAs and methylation on gene expression during the development of chemoresistance.

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Section: Discussioncontrasting

confidence: 79%

Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer

Gao

et al. 2016

Sci Rep

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“…Transfection was carried out as described previously 48 . We performed HEK293T cell transfection with polyethyleneimine (PEI) at a ratio of 4:1 (μl PEI/μg plasmid DAN) in basal media overnight followed by change of media.…”

Section: Methodsmentioning

confidence: 99%

ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation

et al. 2016

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Heat shock protein (Hsp)70 is a molecular chaperone that maintains protein homoeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. However, the mechanisms by which Hsp70 balances these opposing functions under stress conditions remain unknown. Here, we demonstrate that Hsp70 preferentially facilitates protein refolding after stress, gradually switching to protein degradation via a mechanism dependent on ARD1-mediated Hsp70 acetylation. During the early stress response, Hsp70 is immediately acetylated by ARD1 at K77, and the acetylated Hsp70 binds to the co-chaperone Hop to allow protein refolding. Thereafter, Hsp70 is deacetylated and binds to the ubiquitin ligase protein CHIP to complete protein degradation during later stages. This switch is required for the maintenance of protein homoeostasis and ultimately rescues cells from stress-induced cell death in vitro and in vivo. Therefore, ARD1-mediated Hsp70 acetylation is a regulatory mechanism that temporally balances protein refolding/degradation in response to stress.

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“…Transfection. Transfection was carried out as described previously (20). HEk293T cell transfection used polyethyleneimine (PEI) at a ratio of 4:1 (ml PEI/mg plasmid DAN) in basal media overnight, followed by a change of media.…”

Section: Methodsmentioning

confidence: 99%

Hsp70 acetylation prevents caspase-dependent/independent apoptosis and autophagic cell death in cancer cells

Park

Seo

Park

et al. 2017

International Journal of Oncology

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Cancer cells are continuously challenged by adverse environmental factors including hypoxia, metabolite restriction, and immune reactions, and must adopt diverse strategies to survive. Heat shock protein (Hsp) 70 plays a central role in protection against stress-induced cell death by maintaining protein homeostasis and interfering with the process of programmed cell death. Recent findings have suggested that Hsp70 acetylation is a key regulatory modification required for its chaperone activity, but its relevance in the process of programmed cell death and the underlying mechanisms involved are not well understood. In this study, we sought to investigate mechanisms mediated by Hsp70 acetylation in relation to apoptotic and autophagic programmed cell death. Upon stress-induced apoptosis, Hsp70 acetylation inhibits apoptotic cell death, mediated by Hsp70 association with apoptotic protease-activating factor (Apaf)-1 and apoptosis-inducing factor (AIF), key modulators of caspase-dependent and -independent apoptotic pathways, respectively. Hsp70 acetylation also attenuated autophagic cell death associated with upregulation of autophagy-related genes and autophagosome induction. Collectively, these results suggest that the acetylation of Hsp70 plays key regulatory roles in cell death pathways as well as in its function as a chaperone, together enabling cellular protection in response to stress.

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Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury

Cited by 28 publications

References 64 publications

Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer

Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer

ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation

Hsp70 acetylation prevents caspase-dependent/independent apoptosis and autophagic cell death in cancer cells

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