PLoS Articles
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UNC-authored articles published by the Public Library of Science (PLoS)
Works (2111)
1631. Molecular Origin of Polyglutamine Aggregation in Neurodegenerative Diseases
- Title Tesim:
- Molecular Origin of Polyglutamine Aggregation in Neurodegenerative Diseases
- Creator:
- Dokholyan, Nikolay V., Gwanmesia, Kenneth N., Khare, Sagar D., and Ding, Feng
- Date of publication:
- 2005
- Abstract Tesim:
- Expansion of polyglutamine (polyQ) tracts in proteins results in protein aggregation and is associated with cell death in at least nine neurodegenerative diseases. Disease age of onset is correlated with the polyQ insert length above a critical value of 35–40 glutamines. The aggregation kinetics of isolated polyQ peptides in vitro also shows a similar critical-length dependence. While recent experimental work has provided considerable insights into polyQ aggregation, the molecular mechanism of aggregation is not well understood. Here, using computer simulations of isolated polyQ peptides, we show that a mechanism of aggregation is the conformational transition in a single polyQ peptide chain from random coil to a parallel β-helix. This transition occurs selectively in peptides longer than 37 glutamines. In the β-helices observed in simulations, all residues adopt β-strand backbone dihedral angles, and the polypeptide chain coils around a central helical axis with 18.5 ± 2 residues per turn. We also find that mutant polyQ peptides with proline-glycine inserts show formation of antiparallel β-hairpins in their ground state, in agreement with experiments. The lower stability of mutant β-helices explains their lower aggregation rates compared to wild type. Our results provide a molecular mechanism for polyQ-mediated aggregation.
- Resource type:
- Article
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/qerd-6053
- Identifier:
- Onescience id: 00ee593c91effa8b998f9296d6efad9e817b827f, PMID: 16158094, PMCID: PMC1193989, and Publisher DOI: https://doi.org/10.1371/journal.pcbi.0010030
- ISSN:
- 1553-734X and 1553-7358
- Journal Issue:
- 2005
- Journal Title:
- PLoS Computational Biology
- Journal Volume:
- preprint
- Keyword:
- Peptides, Methylenes, Ground state, Hydrogen bonding, Simulation and modeling, Biochemical simulations, Protein aggregation, and Glutamine
- Language Label:
- English
- Page Start:
- e30
- Person:
- Dokholyan, Nikolay V., Gwanmesia, Kenneth N., Khare, Sagar D., and Ding, Feng
- Rights Statement Label:
- In Copyright
- Source:
- 47429h51f
1632. IMPROVE trial: A randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies
- Title Tesim:
- IMPROVE trial: A randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies
- Creator:
- Hsu, Lewis L, Ataga, Kenneth I, Smith, Wally R, McClish, Donna, Molokie, Robert, Osunkwo, Ifeyinwa, Wager, Carrie G, Smith-Whitley, Kim, Weiner, Debra L, McKinlay, Sonja M, Kim, Hae-Young, Krishnamurti, Lakshmanan, Dampier, Carlton D, Eckman, James R, Bell, Margaret C, Telen, Marilyn J, Minniti, Caterina P, and Miller, Scott T
- Date of publication:
- 2013
- Abstract Tesim:
- BACKGROUND: The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The evidence base is lacking for most analgesic practice in SCD, particularly for the optimal opioid dosing for patient-controlled analgesia (PCA), in part because of the challenges of the trial design and conduct for this rare disease. PURPOSE: The purpose of this report is to describe our Network's experiences with protocol development, implementation, and analysis, including overall study design, the value of pain assessments rather than 'crisis' resolution as trial endpoints, and alternative statistical analysis strategies. METHODS: The Improving Pain Management and Outcomes with Various Strategies (IMPROVE) PCA trial was a multisite inpatient randomized controlled trial comparing two PCA-dosing strategies in adults and children with SCD and acute pain conducted by the SCD Clinical Research Network. The specified primary endpoint was a 25-mm change in a daily average pain intensity using a Visual Analogue Scale, and a number of related pain intensity and pain interference measures were selected as secondary efficacy outcomes. A time-to-event analysis strategy was planned for the primary endpoint. RESULTS: Of 1116 individuals admitted for pain at 31 participating sites over a 6-month period, 38 were randomized and 4 withdrawn. The trial was closed early due to poor accrual, reflecting a substantial number of challenges encountered during trial implementation. LIMITATIONS: While some of the design issues were unique to SCD or analgesic studies, many of the trial implementation challenges reflected the increasing complexity of conducting clinical trials in the inpatient setting with multiple care providers and evolving electronic medical record systems, particularly in the context of large urban academic medical centers. LESSONS LEARNED: Complicated clinical organization of many sites likely slowed study initiation. More extensive involvement of research staff and site principal investigator in the clinical care operations improved site performance. During the subsequent data analysis, alternative statistical approaches were considered, the results of which should inform future efficacy assessments and increase future trial recruitment success by allowing substantial reductions in target sample size. CONCLUSIONS: A complex randomized analgesic trial was initiated within a multisite disease network seeking to provide an evidence base for clinical care. A number of design considerations were shown to be feasible in this setting, and several pain intensity and pain interference measures were shown to be sensitive to time- and treatment-related improvements. While the premature closure and small sample size precluded definitive conclusions regarding treatment efficacy, this trial furnishes a template for design and implementation considerations that should improve future SCD analgesic trials.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Medicine
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/ypzk-ej87
- Identifier:
- PMCID: PMC5039779, Onescience id: 5f3ee521cdf09119e27a6c054eb36e3aa51560ae, PMID: 23539110, and Publisher DOI: https://doi.org/10.1177/1740774513475850
- ISSN:
- 1555-5887
- Journal Issue:
- 2
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 10
- Keyword:
- Child, Randomized Controlled Trials as Topic, Research Design, Humans, Adolescent, Pain Management, Anemia, Sickle Cell, Multicenter Studies as Topic, Pain Measurement, Analgesics, Opioid, Pain, Analgesia, Patient-Controlled, and Adult
- Language Label:
- English
- Other Affiliation:
- Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA, Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA, New England Research Institutes, Watertown, MA, USA, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, Children’s Hospital Boston, Boston, MA, USA, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, GA, USA, Department of Medicine, Duke University Medical Center, Durham, NC, USA, and Hematology Branch, National Institutes of Health, Bethesda, MD, USA
- Page End:
- 331
- Page Start:
- 319
- Person:
- Hsu, Lewis L, Ataga, Kenneth I, Smith, Wally R, McClish, Donna, Molokie, Robert, Osunkwo, Ifeyinwa, Wager, Carrie G, Smith-Whitley, Kim, Weiner, Debra L, McKinlay, Sonja M, Kim, Hae-Young, Krishnamurti, Lakshmanan, Dampier, Carlton D, Eckman, James R, Bell, Margaret C, Telen, Marilyn J, Minniti, Caterina P, and Miller, Scott T
- Rights Statement Label:
- In Copyright
- Source:
- jq085s61f
1633. Clinical trials of health information technology interventions intended for patient use: Unique issues and considerations
- Title Tesim:
- Clinical trials of health information technology interventions intended for patient use: Unique issues and considerations
- Creator:
- Song, Mi-Kyung, Bermudez, Christian A, Myers, Brad, Connolly, Mary, Li, Ruosha, DeVito Dabbs, Annette, Begey, Alex, Pilewski, Joseph M, Dew, Mary Amanda, Aubrecht, Jill, and Hawkins, Robert P
- Date of publication:
- 2013
- Abstract Tesim:
- BACKGROUND: Despite the proliferation of health information technology (IT) interventions, descriptions of the unique considerations for conducting randomized trials of health IT interventions intended for patient use are lacking. PURPOSE: Our purpose is to describe the protocol to evaluate Pocket PATH (Personal Assistant for Tracking Health), a novel health IT intervention, as an exemplar of how to address issues that may be unique to a randomized controlled trial (RCT) to evaluate health IT intended for patient use. METHODS: An overview of the study protocol is presented. Unique considerations for health IT intervention trials and strategies are described to maintain equipoise, to monitor data safety and intervention fidelity, and to keep pace with changing technology during such trials. LESSONS LEARNED: The sovereignty granted to technology, the rapid pace of changes in technology, ubiquitous use in health care, and obligation to maintain the safety of research participants challenge researchers to address these issues in ways that maintain the integrity of intervention trials designed to evaluate the impact of health IT interventions intended for patient use. CONCLUSIONS: Our experience evaluating the efficacy of Pocket PATH may provide practical guidance to investigators about how to comply with established procedures for conducting RCTs and include strategies to address the unique issues associated with the evaluation of health IT for patient use.
- Resource type:
- Article
- Affiliation Label Tesim:
- School of Nursing
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/zdd8-th13
- Identifier:
- PMCID: PMC3808467, Onescience id: 0b829e3c33a09b7770de639557d365e44a522b53, Publisher DOI: https://doi.org/10.1177/1740774513493149, and PMID: 23867222
- ISSN:
- 1555-5887
- Journal Issue:
- 6
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 10
- Keyword:
- Humans, Patient Acceptance of Health Care, Attitude to Computers, Self Care, Lung Transplantation, Mobile Applications, Randomized Controlled Trials as Topic, Computers, Handheld, and Medical Informatics
- Language Label:
- English
- Other Affiliation:
- School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA, Human Computer Interaction Institute, Carnegie Mellon University, Pittsburgh, PA, USA, School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, and School of Journalism and Mass Communication, University of Wisconsin–Madison, Madison, WI, USA
- Page End:
- 906
- Page Start:
- 896
- Person:
- Song, Mi-Kyung, Bermudez, Christian A, Myers, Brad, Connolly, Mary, Li, Ruosha, DeVito Dabbs, Annette, Begey, Alex, Pilewski, Joseph M, Dew, Mary Amanda, Aubrecht, Jill, and Hawkins, Robert P
- Rights Statement Label:
- In Copyright
- Source:
- pc289r80s
1634. A surveillance system for monitoring, public reporting, and improving minority access to cancer clinical trials
- Title Tesim:
- A surveillance system for monitoring, public reporting, and improving minority access to cancer clinical trials
- Creator:
- Carpenter, William R, Godley, Paul A, Meyer, Anne-Marie, Wu, Yang, Tyree, Seth, DiMartino, Lisa, and Zullig, Leah
- Date of publication:
- 2012
- Abstract Tesim:
- The Institute of Medicine (IOM) has recommended that each person with cancer should have access to clinical trials, which have been associated with improving care quality and disparities. With no effective enrollment monitoring system, patterns of trial enrollment remain unclear.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Health Policy and Management, Cecil G. Sheps Center for Health Services Research, and UNC Lineberger Comprehensive Cancer Center
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/teva-0034
- Identifier:
- Publisher DOI: https://doi.org/10.1177/1740774512449531, PMID: 22761398, Onescience id: 3d8e81e5e311c9102cdb127289cbd9f5813e5aa8, and PMCID: PMC3539770
- ISSN:
- 1555-5887
- Journal Issue:
- 4
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 9
- Keyword:
- Minority Groups, Population Surveillance, Multivariate Analysis, Male, Female, Adult, North Carolina, Aged, Patient Selection, Randomized Controlled Trials as Topic, Registries, Neoplasms, Healthcare Disparities, Health Services Accessibility, Aged, 80 and over, Humans, and Middle Aged
- Language Label:
- English
- Page End:
- 435
- Page Start:
- 426
- Person:
- Carpenter, William R, Godley, Paul A, Meyer, Anne-Marie, Wu, Yang, Tyree, Seth, DiMartino, Lisa, and Zullig, Leah
- Rights Statement Label:
- In Copyright
- Source:
- 6969z811p
1635. Insights from the conduct of a device trial in older persons: low magnitude mechanical stimulation for musculoskeletal health
- Title Tesim:
- Insights from the conduct of a device trial in older persons: low magnitude mechanical stimulation for musculoskeletal health
- Creator:
- Brown, Kathleen M, Bouxsein, Mary L, Kiel, Douglas P, Rubin, Clinton T, Hannan, Marian T, Magaziner, Jay, Zimmerman, Sheryl, Shane, Elizabeth, Lang, Thomas F, and Barton, Bruce A
- Date of publication:
- 2010
- Abstract Tesim:
- Osteoporosis is a common complication of aging. Alternatives to pharmacologic treatment are needed for older adults. Non-pharmacologic treatment with low magnitude, high frequency mechanical stimulation has been shown to prevent bone loss in animal and human studies.
- Resource type:
- Article
- Affiliation Label Tesim:
- Cecil G. Sheps Center for Health Services Research
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/hswk-wd16
- Identifier:
- PMID: 20571129, Publisher DOI: https://doi.org/10.1177/1740774510371014, Onescience id: 4f836751688ee42af47d12e586c1d9738120bd6d, and PMCID: PMC3136380
- ISSN:
- 1555-5887
- Journal Issue:
- 4
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 7
- Keyword:
- Calcium, Vitamin D, Humans, Dietary Supplements, Postural Balance, Aged, 80 and over, Aged, Biomarkers, Middle Aged, Male, Bone Density, Patient Compliance, Osteoporosis, Vibration, Equipment and Supplies, Research Design, and Female
- Language Label:
- English
- Other Affiliation:
- Maryland Medical Research Institute, Baltimore, MD, USA, Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA, Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA, , Biomedical Engineering, SUNY Stony Brook, Stony Brook, NY, USA, Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA, Epidemiology & Preventive Medicine, University of Maryland, Baltimore, MD, USA, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY, USA, and Radiology, UCSF, San Francisco, CA, USA
- Page End:
- 367
- Page Start:
- 354
- Person:
- Brown, Kathleen M, Bouxsein, Mary L, Kiel, Douglas P, Rubin, Clinton T, Hannan, Marian T, Magaziner, Jay, Zimmerman, Sheryl, Shane, Elizabeth, Lang, Thomas F, and Barton, Bruce A
- Rights Statement Label:
- In Copyright
- Source:
- pc289r791
1636. The Hip Impact Protection Project: design and methods
- Title Tesim:
- The Hip Impact Protection Project: design and methods
- Creator:
- Zimmerman, Sheryl, Magaziner, Jay, Brown, Kathleen M, Birge, Stanley J, Ball, Linda, Barton, Bruce A, and Kiel, Douglas P
- Date of publication:
- 2008
- Abstract Tesim:
- Nearly 340,000 hip fractures occur each year in the U.S. With current demographic trends, the number of hip fractures is expected to double at least in the next 40 years.
- Resource type:
- Article
- Affiliation Label Tesim:
- Cecil G. Sheps Center for Health Services Research
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/9wm0-7d17
- Identifier:
- Publisher DOI: https://doi.org/10.1177/1740774508095120, PMID: 18697849, PMCID: PMC3725461, and Onescience id: e48445e1232bfbae3d9fc2214e83735384e2ba46
- ISSN:
- 1555-5887
- Journal Issue:
- 4
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 5
- Keyword:
- Guideline Adherence, Multicenter Studies as Topic, Humans, Protective Devices, Safety Management, Homes for the Aged, Nursing Homes, Aged, Hip Fractures, Research Design, and Matched-Pair Analysis
- Language Label:
- English
- Other Affiliation:
- Division of Gerontology, Department of Epidemiology and Preventive Medicine, University of Maryland Baltimore, Baltimore, MD, USA, Maryland Medical Research Institute, Baltimore, MD, USA, Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, USA, Maryland Medical Research Institute, Baltimore, MD, USA, , and Institute for Aging Research, Hebrew SeniorLife, and Harvard Medical School, Boston, MA, USA
- Page End:
- 355
- Page Start:
- 347
- Person:
- Zimmerman, Sheryl, Magaziner, Jay, Brown, Kathleen M, Birge, Stanley J, Ball, Linda, Barton, Bruce A, and Kiel, Douglas P
- Rights Statement Label:
- In Copyright
- Source:
- n296x6348
1637. Factors in AIDS Dementia Complex Trial Design: Results and Lessons from the Abacavir Trial
- Title Tesim:
- Factors in AIDS Dementia Complex Trial Design: Results and Lessons from the Abacavir Trial
- Creator:
- Brew, Bruce J, Arthur, Justin C. Mc, Torres, Gabriel, Brown, Steve, Price, Richard W, Sacktor, Ned, Clifford, David B, Hall, Colin, Marder, Karen, Symonds, William, Catalan, Jose, Atkinson, Hamp, Power, Christopher, Halman, Mark, Romero, Carmen, and Simpson, David
- Date of publication:
- 2007
- Abstract Tesim:
- To determine the efficacy of adding abacavir (Ziagen, ABC) to optimal stable background antiretroviral therapy (SBG) to AIDS dementia complex (ADC) patients and address trial design.
- Resource type:
- Article
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/bw5y-x822
- Identifier:
- Publisher DOI: https://doi.org/10.1371/journal.pctr.0020013, PMID: 17401456, PMCID: PMC1845158, and Onescience id: bae231686ea1a0f70d9d1f078ff7b8a47298ca02
- ISSN:
- 1555-5887
- Journal Issue:
- 3
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 2
- Keyword:
- HIV-1, Highly-active antiretroviral therapy, Antiretroviral therapy, Antiretrovirals, Cerebrospinal fluid, HIV, Neuropsychology, and Drug therapy
- Language Label:
- English
- Page Start:
- e13
- Person:
- Brew, Bruce J, Arthur, Justin C. Mc, Torres, Gabriel, Brown, Steve, Price, Richard W, Sacktor, Ned, Clifford, David B, Hall, Colin, Marder, Karen, Symonds, William, Catalan, Jose, Atkinson, Hamp, Power, Christopher, Halman, Mark, Romero, Carmen, and Simpson, David
- Rights Statement Label:
- In Copyright
- Source:
- 5q47rw45h
1638. A Randomized Controlled Pilot Trial of Azithromycin or Artesunate Added to Sulfadoxine-Pyrimethamine as Treatment for Malaria in Pregnant Women
- Title Tesim:
- A Randomized Controlled Pilot Trial of Azithromycin or Artesunate Added to Sulfadoxine-Pyrimethamine as Treatment for Malaria in Pregnant Women
- Creator:
- Alker, Alisa P., Mofolo, Innocent, Kalilani, Linda, Chaponda, Marjorie, Meshnick, Steven R., Rogerson, Stephen J., and Kwiek, Jesse J.
- Date of publication:
- 2007
- Abstract Tesim:
- New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance. We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi.
- Resource type:
- Article
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/88bw-p544
- Identifier:
- Publisher DOI: https://doi.org/10.1371/journal.pone.0001166, PMID: 18000538, PMCID: PMC2048661, and Onescience id: 272a495e908676aed564dbc2577b725ce77445bc
- ISSN:
- 1555-5887
- Journal Issue:
- 11
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 2
- Keyword:
- Adolescent, Pilot Projects, Azithromycin, Middle Aged, Adult, Malaria, Falciparum, Pregnancy Complications, Parasitic, Pregnancy, artesunate, Female, Artemisinins, and Humans
- Language Label:
- English
- Page Start:
- e1166
- Person:
- Alker, Alisa P., Mofolo, Innocent, Kalilani, Linda, Chaponda, Marjorie, Meshnick, Steven R., Rogerson, Stephen J., and Kwiek, Jesse J.
- Rights Statement Label:
- In Copyright
- Source:
- sj139922v
1639. Principles for Strengthening the Integrity of Clinical Research
- Title Tesim:
- Principles for Strengthening the Integrity of Clinical Research
- Creator:
- Ehringhaus, Susan and Korn, David
- Date of publication:
- 2006
- Resource type:
- Article
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/aj1p-2012
- Identifier:
- Onescience id: 8bb2baa5be02a09574685803d1641d33d0dd8f86, PMCID: PMC1488888, Publisher DOI: https://doi.org/10.1371/journal.pctr.0010001, and PMID: 16871323
- ISSN:
- 1555-5887
- Journal Issue:
- 1
- Journal Title:
- PLoS Clinical Trials
- Journal Volume:
- 1
- Keyword:
- Medical ethics, Social research, Medicine and health sciences, Clinical trial reporting, Research integrity, Universities, Clinical trials, and Peer review
- Language Label:
- English
- Page Start:
- e1
- Person:
- Ehringhaus, Susan and Korn, David
- Rights Statement Label:
- In Copyright
- Source:
- j098zk016
1640. Correction: Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1
- Title Tesim:
- Correction: Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1
- Creator:
- Jiang, Bowen, Wang, Yi, Zhang, Tengfei, Chen, Xiufei, Guan, Kun-Liang, Xiong, Yue, Liu, Lixia, Ye, Dan, Lin, Huaipeng, Wang, Shiwen, Xia, Yukun, Wang, Yiping, Yang, Chen, Zhou, Lisha, and Chen, Leilei
- Date of publication:
- 2015
- Abstract Tesim:
- Phosphoglycerate kinase 1 (PGK1) catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. PGK1 plays a key role in coordinating glycolytic energy production with one-carbon metabolism, serine biosynthesis, and cellular redox regulation. Here, we report that PGK1 is acetylated at lysine 220 (K220), which inhibits PGK1 activity by disrupting the binding with its substrate, ADP. We have identified KAT9 and HDAC3 as the potential acetyltransferase and deacetylase, respectively, for PGK1. Insulin promotes K220 deacetylation to stimulate PGK1 activity. We show that the PI3K/AKT/mTOR pathway regulates HDAC3 S424 phosphorylation, which promotes HDAC3-PGK1 interaction and PGK1 K220 deacetylation. Our study uncovers a previously unknown mechanism for the insulin and mTOR pathway in regulation of glycolytic ATP production and cellular redox potential via HDAC3-mediated PGK1 deacetylation.
- Resource type:
- Article
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/n1ve-9q15
- Identifier:
- Onescience id: f6b50584a55747b2665b52a6cb5d7f93ff71a369, PMCID: PMC4565669, PMID: 26356530, and Publisher DOI: https://doi.org/10.1371/journal.pbio.1002243
- ISSN:
- 1544-9173 and 1545-7885
- Journal Issue:
- 9
- Journal Title:
- PLoS Biology
- Journal Volume:
- 13
- Keyword:
- HEK293 Cells, Mice, Inbred BALB C, Glycolysis, TOR Serine-Threonine Kinases, Enzyme Activation, Animals, Carbohydrate Metabolism, Histone Acetyltransferases, Histone Deacetylases, Male, Humans, Adenosine Diphosphate, Acetylation, Nerve Tissue Proteins, Oxidation-Reduction, Signal Transduction, and Phosphoglycerate Kinase
- Language Label:
- English
- Page Start:
- e1002243
- Person:
- Jiang, Bowen, Wang, Yi, Zhang, Tengfei, Chen, Xiufei, Guan, Kun-Liang, Xiong, Yue, Liu, Lixia, Ye, Dan, Lin, Huaipeng, Wang, Shiwen, Xia, Yukun, Wang, Yiping, Yang, Chen, Zhou, Lisha, and Chen, Leilei
- Rights Statement Label:
- In Copyright
- Source:
- ft849021s
Collection Details
- Total items
-
2111
- Size
-
unknown
- Date created
-
February 2, 2022