8 results on '"Perry, Rocco"'
Search Results
2. Histone H4 lysine 16 acetylation regulates cellular lifespan
- Author
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Dang, Weiwei, Steffen, Kristan K., Perry, Rocco, Dorsey, Jean A., Johnson, F. Brad, Shilatifard, Ali, Kaeberlein, Matt, Kennedy, Brian K., and Berger, Shelley L.
- Subjects
Post-translational modification -- Research -- Physiological aspects -- Health aspects ,Methylation -- Health aspects -- Research -- Physiological aspects ,Aging -- Causes of -- Physiological aspects -- Research -- Health aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation ,Physiological aspects ,Research ,Causes of ,Health aspects - Abstract
Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved [NAD.sup.+]-dependent deacetylases or ADP-ribosyltransferases, promote longevity in diverse organisms; however, their molecular mechanisms in ageing regulation remain poorly understood. Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 lysine 16 acetylation and bringing in other silencing proteins. Here we report an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferase, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin., Cells undergo characteristic molecular alterations as organisms age (1,2). Studies in model organisms identify conserved genetic pathways that modulate ageing, such as insulin signalling, oxidative stress tolerance and nutrient sensing [...]
- Published
- 2009
3. MYST protein acetyltransferase activity requires active site lysine autoacetylation
- Author
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Yuan, Hua, Rossetto, Dorine, Mellert, Hestia, Dang, Weiwei, Srinivasan, Madhusudan, Johnson, Jamel, Hodawadekar, Santosh, Ding, Emily C, Speicher, Kaye, Abshiru, Nebiyu, Perry, Rocco, Wu, Jiang, Yang, Chao, Zheng, Y George, Speicher, David W, Thibault, Pierre, Verreault, Alain, Johnson, F Bradley, Berger, Shelley L, Sternglanz, Rolf, McMahon, Steven B, Côté, Jacques, and Marmorstein, Ronen
- Subjects
Histones ,Binding Sites ,Saccharomyces cerevisiae Proteins ,Catalytic Domain ,Lysine ,Humans ,Acetylation ,Crystallography, X-Ray ,Article ,Histone Acetyltransferases - Abstract
The MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site. The structure of hMOF also shows partial occupancy of K274 in the unacetylated form, revealing that the side chain reorients to a position that engages the catalytic glutamate residue and would block cognate protein substrate binding. Consistent with the structural findings, we present mass spectrometry data and biochemical experiments to demonstrate that this lysine autoacetylation on yEsa1, hMOF and its yeast orthologue, ySas2 (KAT8) occurs in solution and is required for acetylation and protein substrate binding in vitro. We also show that this autoacetylation occurs in vivo and is required for the cellular functions of these MYST proteins. These findings provide an avenue for the autoposttranslational regulation of MYST proteins that is distinct from other acetyltransferases but draws similarities to the phosphoregulation of protein kinases.
- Published
- 2011
4. H3K36 methylation promotes longevity by enhancing transcriptional fidelity
- Author
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Sen, Payel, primary, Dang, Weiwei, additional, Donahue, Greg, additional, Dai, Junbiao, additional, Dorsey, Jean, additional, Cao, Xiaohua, additional, Liu, Wei, additional, Cao, Kajia, additional, Perry, Rocco, additional, Lee, Jun Yeop, additional, Wasko, Brian M., additional, Carr, Daniel T., additional, He, Chong, additional, Robison, Brett, additional, Wagner, John, additional, Gregory, Brian D., additional, Kaeberlein, Matt, additional, Kennedy, Brian K., additional, Boeke, Jef D., additional, and Berger, Shelley L., additional
- Published
- 2015
- Full Text
- View/download PDF
5. Yeast Aging Proteome Unveiled a Novel Aging Regulation Pathway Mediated by the Chromatin Remodeling Complex ISW2
- Author
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Dang, Weiwei, primary, Jansen, Pascal, additional, Dorsey, Jean, additional, Cao, Kajia, additional, Perry, Rocco, additional, Kaeberlein, Matt, additional, Kennedy, Brian K, additional, Vermeulen, Michiel, additional, and Berger, Shelley, additional
- Published
- 2012
- Full Text
- View/download PDF
6. MYST protein acetyltransferase activity requires active site lysine autoacetylation
- Author
-
Yuan, Hua, primary, Rossetto, Dorine, additional, Mellert, Hestia, additional, Dang, Weiwei, additional, Srinivasan, Madhusudan, additional, Johnson, Jamel, additional, Hodawadekar, Santosh, additional, Ding, Emily C, additional, Speicher, Kaye, additional, Abshiru, Nebiyu, additional, Perry, Rocco, additional, Wu, Jiang, additional, Yang, Chao, additional, Zheng, Y George, additional, Speicher, David W, additional, Thibault, Pierre, additional, Verreault, Alain, additional, Johnson, F Bradley, additional, Berger, Shelley L, additional, Sternglanz, Rolf, additional, McMahon, Steven B, additional, Côté, Jacques, additional, and Marmorstein, Ronen, additional
- Published
- 2011
- Full Text
- View/download PDF
7. MYST protein acetyltransferase activity requires active site lysine autoacetylation.
- Author
-
Yuan, Hua, Rossetto, Dorine, Mellert, Hestia, Dang, Weiwei, Srinivasan, Madhusudan, Johnson, Jamel, Hodawadekar, Santosh, Ding, Emily C, Speicher, Kaye, Abshiru, Nebiyu, Perry, Rocco, Wu, Jiang, Yang, Chao, Zheng, Y George, Speicher, David W, Thibault, Pierre, Verreault, Alain, Johnson, F Bradley, Berger, Shelley L, and Sternglanz, Rolf
- Subjects
ACETYLTRANSFERASES ,PROTEINS ,BINDING sites ,LYSINE ,ACETYLATION ,EUKARYOTIC cells ,GENETIC regulation - Abstract
The MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site. The structure of hMOF also shows partial occupancy of K274 in the unacetylated form, revealing that the side chain reorients to a position that engages the catalytic glutamate residue and would block cognate protein substrate binding. Consistent with the structural findings, we present mass spectrometry data and biochemical experiments to demonstrate that this lysine autoacetylation on yEsa1, hMOF and its yeast orthologue, ySas2 (KAT8) occurs in solution and is required for acetylation and protein substrate binding in vitro. We also show that this autoacetylation occurs in vivo and is required for the cellular functions of these MYST proteins. These findings provide an avenue for the autoposttranslational regulation of MYST proteins that is distinct from other acetyltransferases but draws similarities to the phosphoregulation of protein kinases. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
8. Histone H4 lysine 16 acetylation regulates cellular lifespan.
- Author
-
Weiwei Dang, Steffen, Kristan K., Perry, Rocco, Dorsey, Jean A., Johnson, F. Brad, Shilatifard, Ali, Kaeberlein, Matt, Kennedy, Brian K., and Berger, Shelley L.
- Subjects
RESEARCH ,CELLS ,HISTONES ,BASIC proteins ,CHROMATIN ,ACETYLATION ,PROTEIN synthesis ,LYSINE - Abstract
Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD
+ -dependent deacetylases or ADP-ribosyltransferases, promote longevity in diverse organisms; however, their molecular mechanisms in ageing regulation remain poorly understood. Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 lysine 16 acetylation and bringing in other silencing proteins. Here we report an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferase, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
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