cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1396275.v3
title: Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy

description: Tafazzin (TAZ) is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mutations of TAZ cause Barth syndrome, which is characterized by mitochondrial dysfunction and dilated cardiomyopathy, leading to premature death. However, the molecular mechanisms underlying the cause of mitochondrial dysfunction in Barth syndrome remain poorly understood. Here we investigated the role of TAZ in regulating mitochondrial function and mitophagy. Using primary mouse embryonic fibroblasts (MEFs) with doxycycline-inducible knockdown of <i>Taz</i>, we showed that TAZ deficiency in MEFs caused defective mitophagosome biogenesis, but not other autophagic processes. Consistent with a key role of mitophagy in mitochondria quality control, TAZ deficiency in MEFs also led to impaired oxidative phosphorylation and severe oxidative stress. Together, these findings provide key insights on mitochondrial dysfunction in Barth syndrome, suggesting that pharmacological restoration of mitophagy may provide a novel treatment for this lethal condition.
DOI: 10.6084/m9.figshare.1396275.v2
title: Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy

description: Tafazzin (TAZ) is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mutations of TAZ cause Barth syndrome, which is characterized by mitochondrial dysfunction and dilated cardiomyopathy, leading to premature death. However, the molecular mechanisms underlying the cause of mitochondrial dysfunction in Barth syndrome remain poorly understood. Here we investigated the role of TAZ in regulating mitochondrial function and mitophagy. Using primary mouse embryonic fibroblasts (MEFs) with doxycycline-inducible knockdown of <i>Taz</i>, we showed that TAZ deficiency in MEFs caused defective mitophagosome biogenesis, but not other autophagic processes. Consistent with a key role of mitophagy in mitochondria quality control, TAZ deficiency in MEFs also led to impaired oxidative phosphorylation and severe oxidative stress. Together, these findings provide key insights on mitochondrial dysfunction in Barth syndrome, suggesting that pharmacological restoration of mitophagy may provide a novel treatment for this lethal condition.
DOI: 10.6084/m9.figshare.1396276
title: Histone deacetylase inhibitors induce autophagy through FOXO1-dependent pathways

description: Autophagy is a catabolic process in response to starvation or other stress conditions to sustain cellular homeostasis. At present, histone deacetylase inhibitors (HDACIs) are known to induce autophagy in cells through inhibition of mechanistic target of rapamycin (MTOR) pathway. FOXO1, an important transcription factor regulated by AKT, is also known to play a role in autophagy induction. At present, the role of FOXO1 in the HDACIs-induced autophagy has not been reported. In this study, we first observed that HDACIs increased the expression of FOXO1 at the mRNA and protein level. Second, we found that FOXO1 transcriptional activity was enhanced by HDACIs, as evidenced by increased FOXO1 nuclear accumulation and transcriptional activity. Third, suppression of FOXO1 function by siRNA knockdown or by a chemical inhibitor markedly blocked HDACIs-induced autophagy. Moreover, we found that FOXO1-mediated autophagy is achieved via its transcriptional activation, leading to a dual effect on autophagy induction: (i) enhanced expression of autophagy-related (<i>ATG</i>) genes, and (ii) suppression of MTOR via transcription of the <i>SESN3</i> (<i>sestrin 3</i>) gene. Finally, we found that inhibition of autophagy markedly enhanced HDACIs-mediated cell death, indicating that autophagy serves as an important cell survival mechanism. Taken together, our studies reveal a novel function of FOXO1 in HDACIs-mediated autophagy in human cancer cells and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in cancer therapy.
DOI: 10.6084/m9.figshare.1396276.v1
title: Histone Deacetylase Inhibitors Induce Autophagy through FOXO1-Dependent Pathways

description: Autophagy is a catabolic process in response to starvation or other stress conditions to sustain cellular homeostasis. At present, histone deacetylase inhibitors (HDACIs) are known to induce autophagy in cells through inhibition of mechanistic target of rapamycin (MTOR) pathway. FOXO1, an important transcription factor regulated by by AKT is also known to play a role in autophagy induction. At present, the role of FOXO1 in the HDACIs-induced autophagy has not been reported. In this study, we first observed that HDACIs increased the expression of FOXO1 at the mRNA and protein level. Second, we found that FOXO1 transcriptional activity was enhanced by HDACIs, as evidenced by increased FOXO1 nuclear accumulation and transcriptional activity. Third, suppression of FOXO1 function by siRNA knockdown or by a chemical inhibitor markedly blocked HDACIs-induced autophagy. Moreover, we found that FOXO1-mediated autophagy is achieved via its transcriptional activation, leading to a dual effect on autophagy induction: (i) enhanced expression of autophagy-related (<i>ATG</i>) genes, and (ii) suppression of MTOR via transcription of the <i>SESN3</i> (<i>sestrin 3</i>) gene. Finally, we found that inhibition of autophagy markedly enhanced HDACIs-mediated cell death, indicating that autophagy serves as an important cell survival mechanism. Taken together, our studies reveal a novel function of FOXO1 in HDACIs-mediated autophagy in human cancer cells and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in cancer therapy.
DOI: 10.6084/m9.figshare.1396276.v3
title: Histone deacetylase inhibitors induce autophagy through FOXO1-dependent pathways

description: Autophagy is a catabolic process in response to starvation or other stress conditions to sustain cellular homeostasis. At present, histone deacetylase inhibitors (HDACIs) are known to induce autophagy in cells through inhibition of mechanistic target of rapamycin (MTOR) pathway. FOXO1, an important transcription factor regulated by AKT, is also known to play a role in autophagy induction. At present, the role of FOXO1 in the HDACIs-induced autophagy has not been reported. In this study, we first observed that HDACIs increased the expression of FOXO1 at the mRNA and protein level. Second, we found that FOXO1 transcriptional activity was enhanced by HDACIs, as evidenced by increased FOXO1 nuclear accumulation and transcriptional activity. Third, suppression of FOXO1 function by siRNA knockdown or by a chemical inhibitor markedly blocked HDACIs-induced autophagy. Moreover, we found that FOXO1-mediated autophagy is achieved via its transcriptional activation, leading to a dual effect on autophagy induction: (i) enhanced expression of autophagy-related (<i>ATG</i>) genes, and (ii) suppression of MTOR via transcription of the <i>SESN3</i> (<i>sestrin 3</i>) gene. Finally, we found that inhibition of autophagy markedly enhanced HDACIs-mediated cell death, indicating that autophagy serves as an important cell survival mechanism. Taken together, our studies reveal a novel function of FOXO1 in HDACIs-mediated autophagy in human cancer cells and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in cancer therapy.
DOI: 10.6084/m9.figshare.1396276.v2
title: Histone deacetylase inhibitors induce autophagy through FOXO1-dependent pathways

description: Autophagy is a catabolic process in response to starvation or other stress conditions to sustain cellular homeostasis. At present, histone deacetylase inhibitors (HDACIs) are known to induce autophagy in cells through inhibition of mechanistic target of rapamycin (MTOR) pathway. FOXO1, an important transcription factor regulated by AKT, is also known to play a role in autophagy induction. At present, the role of FOXO1 in the HDACIs-induced autophagy has not been reported. In this study, we first observed that HDACIs increased the expression of FOXO1 at the mRNA and protein level. Second, we found that FOXO1 transcriptional activity was enhanced by HDACIs, as evidenced by increased FOXO1 nuclear accumulation and transcriptional activity. Third, suppression of FOXO1 function by siRNA knockdown or by a chemical inhibitor markedly blocked HDACIs-induced autophagy. Moreover, we found that FOXO1-mediated autophagy is achieved via its transcriptional activation, leading to a dual effect on autophagy induction: (i) enhanced expression of autophagy-related (<i>ATG</i>) genes, and (ii) suppression of MTOR via transcription of the <i>SESN3</i> (<i>sestrin 3</i>) gene. Finally, we found that inhibition of autophagy markedly enhanced HDACIs-mediated cell death, indicating that autophagy serves as an important cell survival mechanism. Taken together, our studies reveal a novel function of FOXO1 in HDACIs-mediated autophagy in human cancer cells and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in cancer therapy.
DOI: 10.6084/m9.figshare.1402048
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v1
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v2
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v3
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v4
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v5
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v6
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v7
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v8
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v9
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v10
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v11
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v12
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v13
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v14
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v15
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v16
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v17
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v18
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v19
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v20
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v21
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v22
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v23
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v24
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v25
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v26
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.
DOI: 10.6084/m9.figshare.1402048.v27
title: Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

description: In this project, we design a methods to detect novel transcripts integrating ab initio prediction on genomic sequences and filtration with various RNA-seq data. 100 splice sites were selected and RT-PCR on 48 human tissues and cell lines (including a blank negative control) were conducted. The product of the same tissue or cell line were mixed and sequenced with Illumina Mi-seq.