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6. Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases.

Author

Wu, Yinuo, Ma, Biao, Liu, Chang, Li, Dangdang, and Sui, Guangchao

Subjects
HUNTINGTON disease, PHASE separation, ALZHEIMER'S disease, NEURODEGENERATION, PARKINSON'S disease
Abstract

Neurodegenerative diseases are the leading cause of human disability and immensely reduce patients' life span and quality. The diseases are characterized by the functional loss of neuronal cells and share several common pathogenic mechanisms involving the malfunction, structural distortion, or aggregation of multiple key regulatory proteins. Cellular phase separation is the formation of biomolecular condensates that regulate numerous biological processes, including neuronal development and synaptic signaling transduction. Aberrant phase separation may cause protein aggregation that is a general phenomenon in the neuronal cells of patients suffering neurodegenerative diseases. In this review, we summarize the pathological causes of common neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. We discuss the regulation of key amyloidogenic proteins with an emphasis of their aberrant phase separation and aggregation. We also introduce the approaches as potential therapeutic strategies to ameliorate neurodegenerative diseases through intervening protein aggregation. Overall, this review consolidates the research findings of phase separation and aggregation caused by misfolded proteins in a context of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Directed Evolution of 4-Hydroxyphenylpyruvate Biosensors Based on a Dual Selection System.

Author

Du, Hongxuan, Liang, Yaoyao, Li, Jianing, Yuan, Xinyao, Tao, Fenglin, Dong, Chengjie, Shen, Zekai, Sui, Guangchao, and Wang, Pengchao

Subjects
ESCHERICHIA coli, TRANSCRIPTION factors, POSITIVE systems, BIOSENSORS, ACINETOBACTER, SYNTHETIC biology
Abstract

Biosensors based on allosteric transcription factors have been widely used in synthetic biology. In this study, we utilized the Acinetobacter ADP1 transcription factor PobR to develop a biosensor activating the PpobA promoter when bound to its natural ligand, 4-hydroxybenzoic acid (4HB). To screen for PobR mutants responsive to 4-hydroxyphenylpyruvate(HPP), we developed a dual selection system in E. coli. The positive selection of this system was used to enrich PobR mutants that identified the required ligands. The following negative selection eliminated or weakened PobR mutants that still responded to 4HB. Directed evolution of the PobR library resulted in a variant where PobRW177R was 5.1 times more reactive to 4-hydroxyphenylpyruvate than PobRWT. Overall, we developed an efficient dual selection system for directed evolution of biosensors. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Data from β2-adrenoreceptor Signaling Increases Therapy Resistance in Prostate Cancer by Upregulating MCL1

Author

Hassan, Sazzad, primary, Pullikuth, Ashok, primary, Nelson, Kyle C., primary, Flores, Anabel, primary, Karpova, Yelena, primary, Baiz, Daniele, primary, Zhu, Sinan, primary, Sui, Guangchao, primary, Huang, Yue, primary, Choi, Young A., primary, D'Agostino, Ralph, primary, Hemal, Ashok, primary, von Holzen, Urs, primary, Debinski, Waldemar, primary, and Kulik, George, primary

Published
2023
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12. Supplementary Figures 1-5 from β2-adrenoreceptor Signaling Increases Therapy Resistance in Prostate Cancer by Upregulating MCL1

Author

Hassan, Sazzad, primary, Pullikuth, Ashok, primary, Nelson, Kyle C., primary, Flores, Anabel, primary, Karpova, Yelena, primary, Baiz, Daniele, primary, Zhu, Sinan, primary, Sui, Guangchao, primary, Huang, Yue, primary, Choi, Young A., primary, D'Agostino, Ralph, primary, Hemal, Ashok, primary, von Holzen, Urs, primary, Debinski, Waldemar, primary, and Kulik, George, primary

Published
2023
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13. Data from IRP2 Regulates Breast Tumor Growth

Author

Wang, Wei, primary, Deng, Zhiyong, primary, Hatcher, Heather, primary, Miller, Lance D., primary, Di, Xiumin, primary, Tesfay, Lia, primary, Sui, Guangchao, primary, D'Agostino, Ralph B., primary, Torti, Frank M., primary, and Torti, Suzy V., primary

Published
2023
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14. Data from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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19. Supplementary Figure 2 from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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20. Supplementary Figure 1 from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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23. Supplementary Methods, Legends for Tables 1-2, Figures 1-4 from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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24. Supplementary Table 2 from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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25. Supplementary Figure 4 from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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28. Supplementary Figure 3 from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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29. Supplementary Table 1 from Suppression of Tak1 Promotes Prostate Tumorigenesis

Author

Wu, Min, primary, Shi, Lihong, primary, Cimic, Adela, primary, Romero, Lina, primary, Sui, Guangchao, primary, Lees, Cynthia J., primary, Cline, J. Mark, primary, Seals, Darren F., primary, Sirintrapun, Joseph S., primary, McCoy, Thomas P., primary, Liu, Wennuan, primary, Kim, Jin Woo, primary, Hawkins, Gregory A., primary, Peehl, Donna M., primary, Xu, Jianfeng, primary, and Cramer, Scott D., primary

Published
2023
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42. SRSF5 regulates alternative splicing of DMTF1 pre-mRNA through modulating SF1 binding.

Author

Li, Jialiang, Li, Guangyue, Qi, Yige, Lu, Yao, Wang, Hao, Shi, Ke, Li, Dangdang, Shi, Jinming, Stovall, Daniel B., and Sui, Guangchao

Subjects
ALTERNATIVE RNA splicing, GENE enhancers, NUCLEOPROTEINS, CYCLIN-dependent kinase inhibitors, NUCLEOTIDE sequence, RNA sequencing, PROTEIN binding
Abstract

Among the three DMTF1 splicing isoforms, DMTF1α acts as a tumour suppressor through promoting p14ARF expression, while DMTF1β exhibits an oncogenic role likely through antagonizing DMTF1α. However, the molecular mechanism underlying alternative splicing of DMTF1 pre-mRNA has not been delineated. In the current study, we discovered SRSF5 as a regulatory protein binding to a region located between DMTF1β and α acceptor splice sites to promote DMTF1β and γ splicing. We demonstrated that SRSF5 expression positively correlated with DMTF1β/α ratio in breast cancer samples, and ectopically expressed SRSF5 promoted the splicing of DMTF1β and γ, but not DMTF1α, when testing endogenous DMTF1 pre-mRNA and a reporter construct. Upon SRSF5 knockdown, we observed significantly decreased DMTF1β and γ ratios of endogenous transcripts. An RNA sequence just upstream of the α acceptor site contains two adjacent SRSF5 binding elements, one of which overlaps with an SF1 binding site. Our mechanistic studies revealed that SRSF5 binding to both elements in this region could consign SF1 to its distal-binding sites close to the β and γ acceptor sites, favouring splicing of their isoforms. Overall, our study revealed SRSF5 as a key regulator to promote DMTF1β and γ splicing, and consequently reduce DMTF1α splicing. ARF: alternative reading frame, that is, p14ARF, or CDKN2A (cyclin-dependent kinase inhibitor 2A); β-gal: β-galactosidase; CLIP-seq: crosslinking and immunoprecipitation-sequencing; DMTF1: the cyclin D binding myb-like transcription factor 1; ESS/ESE: exonic splicing silencer/enhancer; Ex: exon; FBS: fetal bovine serum; Gluc: Gaussia luciferase; hnRNPs: heterogeneous nuclear ribonucleoproteins; In: intron; ISS/ISE: intronic splicing silencer/enhancer; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; PSI: percent-splice-in; qPCR: quantitative real-time PCR; RIP: RNA immunoprecipitation; RNAseq: RNA sequencing; RT: reverse transcription; SF1: splicing factor 1; SR: serine/arginine-rich proteins; SRSF5: serine and arginine-rich splicing factor 5; TCGA: the cancer genome atlas; UCSC: University of California, Santa Cruz. WT: Wild type [ABSTRACT FROM AUTHOR]

Published
2023
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43. Directed Evolution of The PobR Allosteric Transcription Factor To Generate A Biosensor For 4-Hydroxymandelic Acid

Author

Liang, YaoYao, primary, Luo, Juan, additional, Yang, Chenhao, additional, Guo, Shuning, additional, Zhang, Bowen, additional, Chen, Fengqianrui, additional, Su, Kairui, additional, Zhang, Yulong, additional, Dong, Yi, additional, Wang, Zhihao, additional, Fu, Hongda, additional, Sui, Guangchao, additional, and Wang, Pengchao, additional

Published
2021
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