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  1. Article ; Online: Unraveling the complex relationship between mRNA and protein abundances: a machine learning-based approach for imputing protein levels from RNA-seq data.

    Prabahar, Archana / Zamora, Ruben / Barclay, Derek / Yin, Jinling / Ramamoorthy, Mahesh / Bagheri, Atefeh / Johnson, Scott A / Badylak, Stephen / Vodovotz, Yoram / Jiang, Peng

    NAR genomics and bioinformatics

    2024  Volume 6, Issue 1, Page(s) lqae019

    Abstract: The correlation between messenger RNA (mRNA) and protein abundances has long been debated. RNA sequencing (RNA-seq), a high-throughput, commonly used method for analyzing transcriptional dynamics, leaves questions about whether we can translate RNA-seq- ... ...

    Abstract The correlation between messenger RNA (mRNA) and protein abundances has long been debated. RNA sequencing (RNA-seq), a high-throughput, commonly used method for analyzing transcriptional dynamics, leaves questions about whether we can translate RNA-seq-identified gene signatures directly to protein changes. In this study, we utilized a set of 17 widely assessed immune and wound healing mediators in the context of canine volumetric muscle loss to investigate the correlation of mRNA and protein abundances. Our data reveal an overall agreement between mRNA and protein levels on these 17 mediators when examining samples from the same experimental condition (e.g. the same biopsy). However, we observed a lack of correlation between mRNA and protein levels for individual genes under different conditions, underscoring the challenges in converting transcriptional changes into protein changes. To address this discrepancy, we developed a machine learning model to predict protein abundances from RNA-seq data, achieving high accuracy. Our approach also effectively corrected multiple extreme outliers measured by antibody-based protein assays. Additionally, this model has the potential to detect post-translational modification events, as shown by accurately estimating activated transforming growth factor β1 levels. This study presents a promising approach for converting RNA-seq data into protein abundance and its biological significance.
    Language English
    Publishing date 2024-02-10
    Publishing country England
    Document type Journal Article
    ISSN 2631-9268
    ISSN (online) 2631-9268
    DOI 10.1093/nargab/lqae019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Loss of ATRX Suppresses Resolution of Telomere Cohesion to Control Recombination in ALT Cancer Cells.

    Ramamoorthy, Mahesh / Smith, Susan

    Cancer cell

    2015  Volume 28, Issue 3, Page(s) 357–369

    Abstract: The chromatin-remodeler ATRX is frequently lost in cancer cells that use ALT (alternative lengthening of telomeres) for telomere maintenance, but its function in telomere recombination is unknown. Here we show that loss of ATRX suppresses the timely ... ...

    Abstract The chromatin-remodeler ATRX is frequently lost in cancer cells that use ALT (alternative lengthening of telomeres) for telomere maintenance, but its function in telomere recombination is unknown. Here we show that loss of ATRX suppresses the timely resolution of sister telomere cohesion that normally occurs prior to mitosis. In the absence of ATRX, the histone variant macroH2A1.1 binds to the poly(ADP-ribose) polymerase tankyrase 1, preventing it from localizing to telomeres and resolving cohesion. The resulting persistent telomere cohesion promotes recombination between sister telomeres, while it suppresses inappropriate recombination between non-sisters. Forced resolution of sister telomere cohesion induces excessive recombination between non-homologs, genomic instability, and impaired cell growth, indicating the ATRX-macroH2A1.1-tankyrase axis as a potential therapeutic target in ALT tumors.
    MeSH term(s) Cell Line ; Cell Line, Tumor ; Chromatin Assembly and Disassembly/genetics ; DNA Helicases/genetics ; Genomic Instability/genetics ; HEK293 Cells ; HeLa Cells ; Histones/genetics ; Humans ; Nuclear Proteins/genetics ; Poly(ADP-ribose) Polymerases/genetics ; Recombination, Genetic/genetics ; Telomerase/genetics ; Telomere/genetics ; Telomere Homeostasis/genetics ; X-linked Nuclear Protein
    Chemical Substances Histones ; Nuclear Proteins ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Telomerase (EC 2.7.7.49) ; DNA Helicases (EC 3.6.4.-) ; ATRX protein, human (EC 3.6.4.12) ; X-linked Nuclear Protein (EC 3.6.4.12)
    Language English
    Publishing date 2015-09-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2015.08.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Immature mDA neurons ameliorate motor deficits in a 6-OHDA Parkinson's disease mouse model and are functional after cryopreservation.

    Leitner, Dominique / Ramamoorthy, Mahesh / Dejosez, Marion / Zwaka, Thomas P

    Stem cell research

    2019  Volume 41, Page(s) 101617

    Abstract: Parkinson's disease is associated with the loss of dopaminergic neurons in the midbrain. Clinical studies investigating replacement of these neurons with in vitro-generated neurons are currently underway. However, this approach has been limited by ... ...

    Abstract Parkinson's disease is associated with the loss of dopaminergic neurons in the midbrain. Clinical studies investigating replacement of these neurons with in vitro-generated neurons are currently underway. However, this approach has been limited by difficulties in scaling up on-demand production of midbrain dopaminergic (mDA) neurons from pluripotent stem cells. Cryo-preservation may offer a solution, as it allows for banking of quality controlled mDA neurons. In this study, we tested different freezing conditions and found that optimal cryopreservation of immature human mDA neurons at an early differentiation time point was achieved in STEM-CELLBANKER medium using a controlled freezing program.
    MeSH term(s) Animals ; Cell Differentiation ; Cell Line ; Cryopreservation ; Dopaminergic Neurons/metabolism ; Dopaminergic Neurons/pathology ; Dopaminergic Neurons/transplantation ; Heterografts ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology ; Mesencephalon/metabolism ; Mesencephalon/pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Oxidopamine/pharmacology ; Parkinson Disease, Secondary/chemically induced ; Parkinson Disease, Secondary/metabolism ; Parkinson Disease, Secondary/pathology ; Parkinson Disease, Secondary/therapy
    Chemical Substances Oxidopamine (8HW4YBZ748)
    Language English
    Publishing date 2019-10-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1876-7753
    ISSN (online) 1876-7753
    DOI 10.1016/j.scr.2019.101617
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  4. Article ; Online: Regulatory architecture of housekeeping genes is driven by promoter assemblies.

    Dejosez, Marion / Dall'Agnese, Alessandra / Ramamoorthy, Mahesh / Platt, Jesse / Yin, Xing / Hogan, Megan / Brosh, Ran / Weintraub, Abraham S / Hnisz, Denes / Abraham, Brian J / Young, Richard A / Zwaka, Thomas P

    Cell reports

    2023  Volume 42, Issue 5, Page(s) 112505

    Abstract: Genes that are key to cell identity are generally regulated by cell-type-specific enhancer elements bound by transcription factors, some of which facilitate looping to distant gene promoters. In contrast, genes that encode housekeeping functions, whose ... ...

    Abstract Genes that are key to cell identity are generally regulated by cell-type-specific enhancer elements bound by transcription factors, some of which facilitate looping to distant gene promoters. In contrast, genes that encode housekeeping functions, whose regulation is essential for normal cell metabolism and growth, generally lack interactions with distal enhancers. We find that Ronin (Thap11) assembles multiple promoters of housekeeping and metabolic genes to regulate gene expression. This behavior is analogous to how enhancers are brought together with promoters to regulate cell identity genes. Thus, Ronin-dependent promoter assemblies provide a mechanism to explain why housekeeping genes can forgo distal enhancer elements and why Ronin is important for cellular metabolism and growth control. We propose that clustering of regulatory elements is a mechanism common to cell identity and housekeeping genes but is accomplished by different factors binding distinct control elements to establish enhancer-promoter or promoter-promoter interactions, respectively.
    MeSH term(s) Genes, Essential/genetics ; Enhancer Elements, Genetic/genetics ; Transcription Factors/metabolism ; Promoter Regions, Genetic/genetics
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2023-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112505
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  5. Article ; Online: RECQL5 plays co-operative and complementary roles with WRN syndrome helicase.

    Popuri, Venkateswarlu / Huang, Jing / Ramamoorthy, Mahesh / Tadokoro, Takashi / Croteau, Deborah L / Bohr, Vilhelm A

    Nucleic acids research

    2017  Volume 45, Issue 3, Page(s) 1566

    Abstract: Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at ... ...

    Abstract Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. RECQL5 co-operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes. Both RECQL5 and WRN re-localize from the nucleolus into the nucleus after replicative stress and significantly associate with each other during S-phase. Further, we show that RECQL5 is essential for cell survival in the absence of WRN. Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death. Collectively, our results indicate that RECQL5 plays both co-operative and complementary roles with WRN. This is an early demonstration of a significant functional interplay and a novel synthetic lethal interaction among the human RecQ helicases.
    Language English
    Publishing date 2017-02-09
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkw1216
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin.

    Elagooz, Reem / Dhara, Anita R / Gott, Rose M / Adams, Sarah E / White, Rachael A / Ghosh, Arnab / Ganguly, Shinjini / Man, Yuncheng / Owusu-Ansah, Amma / Mian, Omar Y / Gurkan, Umut A / Komar, Anton A / Ramamoorthy, Mahesh / Gnanapragasam, Merlin Nithya

    Blood advances

    2022  Volume 6, Issue 23, Page(s) 6016–6022

    Abstract: The fetal-to-adult hemoglobin switching at about the time of birth involves a shift in expression from γ-globin to β-globin in erythroid cells. Effective re-expression of fetal γ-globin can ameliorate sickle cell anemia and β-thalassemia. Despite the ... ...

    Abstract The fetal-to-adult hemoglobin switching at about the time of birth involves a shift in expression from γ-globin to β-globin in erythroid cells. Effective re-expression of fetal γ-globin can ameliorate sickle cell anemia and β-thalassemia. Despite the physiological and clinical relevance of this switch, its posttranscriptional regulation is poorly understood. Here, we identify Pumilo 1 (PUM1), an RNA-binding protein with no previously reported functions in erythropoiesis, as a direct posttranscriptional regulator of β-globin switching. PUM1, whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin messenger RNA (mRNA), and reduces γ-globin (HBG1) mRNA stability and translational efficiency, which culminates in reduced γ-globin protein levels. Knockdown of PUM1 leads to a robust increase in fetal hemoglobin (∼22% HbF) without affecting β-globin levels in human erythroid cells. Importantly, targeting PUM1 does not limit the progression of erythropoiesis, which provides a potentially safe and effective treatment strategy for sickle cell anemia and β-thalassemia. In support of this idea, we report elevated levels of HbF in the absence of anemia in an individual with a novel heterozygous PUM1 mutation in the RNA-binding domain (p.(His1090Profs∗16); c.3267_3270delTCAC), which suggests that PUM1-mediated posttranscriptional regulation is a critical player during human hemoglobin switching.
    MeSH term(s) Adult ; Humans ; Fetal Hemoglobin/genetics ; Fetal Hemoglobin/metabolism ; gamma-Globins/genetics ; gamma-Globins/metabolism ; beta-Thalassemia/genetics ; beta-Globins/genetics ; Carrier Proteins ; Anemia, Sickle Cell/genetics ; RNA-Binding Proteins/genetics
    Chemical Substances Fetal Hemoglobin (9034-63-3) ; gamma-Globins ; beta-Globins ; Carrier Proteins ; PUM1 protein, human ; RNA-Binding Proteins
    Language English
    Publishing date 2022-06-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2021006730
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  7. Article ; Online: Measurement of chemosensitivity and growth rate in p53 expressing cells.

    Ramamoorthy, Mahesh / Vaughan, Catherine / Deb, Sumitra / Deb, Swati Palit

    Methods in molecular biology (Clifton, N.J.)

    2013  Volume 962, Page(s) 127–133

    Abstract: Chemoresistance and increased growth rate are two gain-of-function functions that mutant p53 is thought to possess. Here, we describe two methods for measuring the sensitiveness of cells to chemotherapeutic drugs and the rate of cell growth. Both of ... ...

    Abstract Chemoresistance and increased growth rate are two gain-of-function functions that mutant p53 is thought to possess. Here, we describe two methods for measuring the sensitiveness of cells to chemotherapeutic drugs and the rate of cell growth. Both of which can be used with a wide range of cell types. The clonogenic assay can be used with many different chemotoxic drugs and the growth assay described here presents an alternative to the MTT assay and allows for a long-term measurement of cell growth. These protocols are both easy, flexible, require relatively little effort, and are inexpensive to carry out.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Cycle/drug effects ; Cell Proliferation/drug effects ; Colony-Forming Units Assay/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Antineoplastic Agents ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2013
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-236-0_10
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  8. Article ; Online: RECQL5 plays co-operative and complementary roles with WRN syndrome helicase.

    Popuri, Venkateswarlu / Huang, Jing / Ramamoorthy, Mahesh / Tadokoro, Takashi / Croteau, Deborah L / Bohr, Vilhelm A

    Nucleic acids research

    2012  Volume 41, Issue 2, Page(s) 881–899

    Abstract: Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at ... ...

    Abstract Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. RECQL5 co-operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes. Both RECQL5 and WRN re-localize from the nucleolus into the nucleus after replicative stress and significantly associate with each other during S-phase. Further, we show that RECQL5 is essential for cell survival in the absence of WRN. Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death. Collectively, our results indicate that RECQL5 plays both co-operative and complementary roles with WRN. This is an early demonstration of a significant functional interplay and a novel synthetic lethal interaction among the human RecQ helicases.
    MeSH term(s) Cell Line ; Cell Survival ; DNA Breaks, Double-Stranded ; DNA Replication ; Exodeoxyribonucleases/metabolism ; Exodeoxyribonucleases/physiology ; Genomic Instability ; RecQ Helicases/antagonists & inhibitors ; RecQ Helicases/metabolism ; RecQ Helicases/physiology ; Werner Syndrome/genetics ; Werner Syndrome Helicase
    Chemical Substances RECQL5 protein, human ; Exodeoxyribonucleases (EC 3.1.-) ; Bloom syndrome protein (EC 3.6.1.-) ; RecQ Helicases (EC 3.6.4.12) ; WRN protein, human (EC 3.6.4.12) ; Werner Syndrome Helicase (EC 3.6.4.12)
    Language English
    Publishing date 2012-11-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gks1134
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  9. Article ; Online: The RecQ helicase RECQL5 participates in psoralen-induced interstrand cross-link repair.

    Ramamoorthy, Mahesh / May, Alfred / Tadokoro, Takashi / Popuri, Venkateswarlu / Seidman, Michael M / Croteau, Deborah L / Bohr, Vilhelm A

    Carcinogenesis

    2013  Volume 34, Issue 10, Page(s) 2218–2230

    Abstract: Interstrand cross-links (ICLs) are very severe lesions as they are absolute blocks of replication and transcription. This property of interstrand cross-linking agents has been exploited clinically for the treatment of cancers and other diseases. ICLs are ...

    Abstract Interstrand cross-links (ICLs) are very severe lesions as they are absolute blocks of replication and transcription. This property of interstrand cross-linking agents has been exploited clinically for the treatment of cancers and other diseases. ICLs are repaired in human cells by specialized DNA repair pathways including components of the nucleotide excision repair pathway, double-strand break repair pathway and the Fanconi anemia pathway. In this report, we identify the role of RECQL5, a member of the RecQ family of helicases, in the repair of ICLs. Using laser-directed confocal microscopy, we demonstrate that RECQL5 is recruited to ICLs formed by trioxalen (a psoralen-derived compound) and ultraviolet irradiation A. Using single-cell gel electrophoresis and proliferation assays, we identify the role of RECQL5 in the repair of ICL lesions. The domain of RECQL5 that recruits to the site of ICL was mapped to the KIX region between amino acids 500 and 650. Inhibition of transcription and of topoisomerases did not affect recruitment, which was inhibited by DNA-intercalating agents, suggesting that the DNA structure itself may be responsible for the recruitment of RECQL5 to the sites of ICLs.
    MeSH term(s) Cell Line ; Cross-Linking Reagents/toxicity ; DNA Damage/drug effects ; DNA Repair/physiology ; DNA Topoisomerases/metabolism ; Exodeoxyribonucleases/metabolism ; Ficusin/toxicity ; Humans ; Kinetics ; Protein Binding ; Protein Interaction Domains and Motifs ; RecQ Helicases/chemistry ; RecQ Helicases/metabolism ; Topoisomerase Inhibitors/pharmacology ; Transcription, Genetic ; Werner Syndrome Helicase
    Chemical Substances Cross-Linking Reagents ; RECQL5 protein, human ; Topoisomerase Inhibitors ; Exodeoxyribonucleases (EC 3.1.-) ; Bloom syndrome protein (EC 3.6.1.-) ; RecQ Helicases (EC 3.6.4.12) ; WRN protein, human (EC 3.6.4.12) ; Werner Syndrome Helicase (EC 3.6.4.12) ; DNA Topoisomerases (EC 5.99.1.-) ; Ficusin (KTZ7ZCN2EX)
    Language English
    Publishing date 2013-05-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 603134-1
    ISSN 1460-2180 ; 0143-3334
    ISSN (online) 1460-2180
    ISSN 0143-3334
    DOI 10.1093/carcin/bgt183
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  10. Article ; Online: MDM2 controls the timely expression of cyclin A to regulate the cell cycle.

    Frum, Rebecca / Ramamoorthy, Mahesh / Mohanraj, Lathika / Deb, Sumitra / Deb, Swati Palit

    Molecular cancer research : MCR

    2009  Volume 7, Issue 8, Page(s) 1253–1267

    Abstract: Overexpression of MDM2 has been related to oncogenesis. In this communication, we present evidence to show that MDM2 controls the cell cycle-dependent expression of cyclin A by using a pathway that ensures its timely expression. MDM2 does not inhibit ... ...

    Abstract Overexpression of MDM2 has been related to oncogenesis. In this communication, we present evidence to show that MDM2 controls the cell cycle-dependent expression of cyclin A by using a pathway that ensures its timely expression. MDM2 does not inhibit cyclin D or E expression. Silencing of endogenous MDM2 expression elevates cyclin A expression. The p53-binding domain of MDM2 harbors a SWIB region homologous to a conserved domain of a chromosome remodeling factor BRG1-associated protein. The SWIB domain of MDM2 inhibits cyclin A expression in a p53- and BRG1-dependent fashion, suggesting that MDM2 interferes with p53 binding of the BRG1 complex freeing it to repress cyclin A expression. Silencing of cyclin-dependent kinase (cdk) inhibitor p16 prevents MDM2-mediated inhibition of cyclin A expression, implicating its role in the process. MDM2-mediated repression of cyclin A expression induces G(1)-S arrest, which can be rescued by ectopic expression of cyclin A. Cancer cells lacking p53, p16, or BRG1 escape MDM2-mediated repression of cyclin A expression and growth arrest. Our data propose a novel mechanism by which MDM2 controls the cell cycle in normal cells and how cancer cells may escape this important safety barrier.
    MeSH term(s) Cell Cycle ; Cell Line, Transformed ; Cell Line, Tumor ; Cyclin A/metabolism ; Cyclin E/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; DNA Helicases/metabolism ; Down-Regulation ; Flow Cytometry ; G1 Phase ; Humans ; Microscopy, Confocal ; Models, Biological ; Nuclear Proteins/metabolism ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-mdm2/chemistry ; Proto-Oncogene Proteins c-mdm2/metabolism ; Time Factors ; Transcription Factors/metabolism ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Cyclin A ; Cyclin E ; Cyclin-Dependent Kinase Inhibitor p16 ; Nuclear Proteins ; Transcription Factors ; Tumor Suppressor Protein p53 ; MDM2 protein, human (EC 2.3.2.27) ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27) ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
    Language English
    Publishing date 2009-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-08-0334
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