Research Topics
Genomes and Genes
| Nikolai TimchenkoSummaryAffiliation: Baylor College of Medicine Country: USA Publications
Research Grants
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Detail Information
Publications
Regenerating livers of old rats contain high levels of C/EBPalpha that correlate with altered expression of cell cycle associated proteinsN A Timchenko
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Nucleic Acids Res 26:3293-9. 1998..We suggest that the failure to reduce the amount of C/EBPalpha and p21 is a critical event in the dysregulation of hepatocyte proliferation in old animals following PH...- C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn miceN A Timchenko
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
Mol Cell Biol 19:2936-45. 1999..The disruption of E2F-p107 complexes correlates with C/EBPalpha-mediated growth arrest of hepatocytes in newborn animals... - E2F/p107 and E2F/p130 complexes are regulated by C/EBPalpha in 3T3-L1 adipocytesN A Timchenko
Huffington Center on Aging, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Nucleic Acids Res 27:3621-30. 1999..Our data suggest two pathways of C/EBPalpha-dependent regulation of E2F/Rb family complexes: disruption of S phase-specific E2F/p107 complexes and induction of E2F/p130 complexes... - CUG repeat binding protein (CUGBP1) interacts with the 5' region of C/EBPbeta mRNA and regulates translation of C/EBPbeta isoformsN A Timchenko
Huffington Center on Aging, Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
Nucleic Acids Res 27:4517-25. 1999..Our data demonstrate that CUGBP1 protein is an important component for the regulation of initiation from different AUG codons of C/EBPbeta mRNA... - Aging and liver regenerationNikolai A Timchenko
Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA
Trends Endocrinol Metab 20:171-6. 2009..This review focuses on mechanisms of age-dependent inhibition of liver proliferation and approaches for correcting liver regeneration in the elderly... - Old livers--C/EBPalpha meets new partnersNikolai A Timchenko
Huffington Center on Aging and Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
Cell Cycle 2:445-6. 2003..This switch causes a loss of proliferative response in old livers because of an inability to induce E2F target genes after partial hepatectomy... - RNA Foci, CUGBP1, and ZNF9 are the primary targets of the mutant CUG and CCUG repeats expanded in myotonic dystrophies type 1 and type 2Karlie Jones
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA
Am J Pathol 179:2475-89. 2011..These data suggest that correction of DM1 and DM2 might be achieved by complete and efficient degradation of CUG and CCUG repeats or by a simultaneous disruption of CUG/CCUG foci and correction of CUGBP1 and ZNF9... - Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during agingRoy G Smith
Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, MS BCM M230, Houston, TX 77030, USA
Ann N Y Acad Sci 1119:147-64. 2007..We speculate that aging is associated with deficient endogenous ghrelin signaling that can be rescued by intervention with GHS-R1a agonists to improve quality of life and maintain independence... - Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cellsClaudia Huichalaf
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
FASEB J 24:3706-19. 2010..The repression of protein translation by stress might contribute to the progressive muscle loss in DM1... - The low molecular weight cyclin E isoforms augment angiogenesis and metastasis of human melanoma cells in vivoElise Bales
Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Cancer Res 65:692-7. 2005..Together, these results indicate that the LMW cyclin E forms are functional and likely act as regulators of human melanoma tumor progression and invasion... - Iron-mediated regulation of liver hepcidin expression in rats and mice is abolished by alcoholDuygu Dee Harrison-Findik
Division of Gastroenterology Hepatology, Department of Internal Medicine, Houston, TX, USA
Hepatology 46:1979-85. 2007..Our findings therefore suggest that alcohol negates the protective effect of hepcidin, which may have implications for the liver injury observed in alcoholic liver disease and genetic hemochromatosis in combination with alcohol... - Calreticulin interacts with C/EBPalpha and C/EBPbeta mRNAs and represses translation of C/EBP proteinsLubov T Timchenko
Department of Pathology and Huffington Center on Aging Departments of Medicine and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA
Mol Cell Biol 22:7242-57. 2002..CRT-dependent inhibition of C/EBPalpha is sufficient to block the growth-inhibitory activity of C/EBPalpha. This finding further defines the molecular mechanism for posttranscriptional regulation of the C/EBPalpha and C/EBPbeta proteins... - Increased CUG triplet repeat-binding protein-1 predisposes to impaired adipogenesis with agingIordanes Karagiannides
Medicine and Biochemistry, Boston University, Boston, Massachusetts 02118, USA
J Biol Chem 281:23025-33. 2006..Altered translational processing, possibly related to changes in cytokine milieu and activation of stress responses, may contribute to changes in progenitor differentiation and tissue function with aging... - Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-binding protein beta in old liverLubov T Timchenko
Huffington Center on Aging and Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
J Biol Chem 281:32806-19. 2006..Thus, these studies demonstrated that age-mediated induction of the CUGBP1-eIF2 complex changes translation of C/EBPbeta in old livers... - Growth hormone corrects proliferation and transcription of phosphoenolpyruvate carboxykinase in livers of old mice via elimination of CCAAT/enhancer-binding protein alpha-Brm complexGuo Li Wang
Huffington Center on Aging and Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 282:1468-78. 2007..GH-dependent elimination of the complex is mediated by the inhibition of cyclin D3-CDK4 activity and by elevation of a phosphatase, protein phosphatase 2A, which dephosphorylates C/EBPalpha and dissociates the complex... - Regulation of the promoter of CUG triplet repeat binding protein, Cugbp1, during myogenesisClaudia H Huichalaf
Department of Medicine, Section of Cardiovascular Sciences, Baylor College of Medicine, One Baylor Plaza, Houston Texas 77030, USA
Gene 396:391-402. 2007..These data show that transcription of Cugbp1 gene in muscle is regulated by myogenin and E proteins and suggest that the co-operation of several transcription factors is important for the activation of the Cugbp1 promoter... - C/EBPbeta suppression by interruption of CUGBP1 resulting from a complex rearrangement of MLLWilliam T Choi
Division of Pediatrics, Cell Therapy Section, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Pediatrics Research Unit 853, Houston, TX 77030 4009, USA
Cancer Genet Cytogenet 177:108-14. 2007..This is the first report to describe insertional disruption of the CUGBP1 gene and to suggest a role for the CUGBP1-C/EBPbeta pathway in leukemogenesis... - Regulation of apoptotic and growth inhibitory activities of C/EBPalpha in different cell linesGuo Li Wang
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Exp Cell Res 314:1626-39. 2008..These data show that apoptotic and growth inhibitory activities of C/EBPalpha are differentially regulated in different cells and that cooperation of cyclin D3 and C/EBPalpha is required for the inhibition of proliferation... - HDAC1 promotes liver proliferation in young mice via interactions with C/EBPbetaGuo Li Wang
Huffington Center on Aging and Department of Pathology, Department of Medicine, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 283:26179-87. 2008..Thus, these studies have identified a new pathway that promotes liver proliferation in young mice and might contribute to the malignant transformations in the liver... - HDAC1 cooperates with C/EBPalpha in the inhibition of liver proliferation in old miceGuo Li Wang
Huffington Center on Aging and Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 283:26169-78. 2008..Thus, our data demonstrate that translational elevation of HDAC1 in livers of old mice is involved in the assembly of high M(r) protein-protein complexes that inhibit liver proliferation... - C/EBPalpha triggers proteasome-dependent degradation of cdk4 during growth arrestHongmei Wang
Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
EMBO J 21:930-41. 2002..Our studies show that C/EBPalpha disrupts the cdk4-cdc37-Hsp90 complex via direct interaction with cdk4 and reduces protein levels of cdk4 by increasing proteasome-dependent degradation of cdk4... - Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expressionDuygu Dee Harrison-Findik
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198 5820, USA
J Biol Chem 281:22974-82. 2006..Collectively, these findings indicate that alcohol metabolism-mediated oxidative stress regulates hepcidin transcription via C/EBPalpha, which in turn leads to increased duodenal iron transport... - Cyclin D3 maintains growth-inhibitory activity of C/EBPalpha by stabilizing C/EBPalpha-cdk2 and C/EBPalpha-Brm complexesGuo Li Wang
Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Mol Cell Biol 26:2570-82. 2006..The inhibition of cyclin D3 blocks the formation of these complexes. Thus, these studies provide a new function of cyclin D3, which is to support the growth-inhibitory activity of C/EBPalpha... - Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrestPolina Iakova
Huffington Center on Aging, Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
Cell 113:495-506. 2003.... - C/EBPalpha is required for proteolytic cleavage of cyclin A by calpain 3 in myeloid precursor cellsAlana L Welm
Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
J Biol Chem 277:33848-56. 2002..These data reveal a new pathway involving tightly controlled post-translational processing of cyclin A during differentiation of granulocytes... - Overexpression of CUG triplet repeat-binding protein, CUGBP1, in mice inhibits myogenesisNikolai A Timchenko
Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
J Biol Chem 279:13129-39. 2004..Our data suggest that CUGBP1-mediated overexpression of MEF2A and p21 inhibits myogenesis and contributes to the development of muscle deficiency in DM1 patients... - Competition of CUGBP1 and calreticulin for the regulation of p21 translation determines cell fatePolina Iakova
Department of Pathology and Huffington Center on Aging, Houston, TX, USA
EMBO J 23:406-17. 2004..These data present evidence that competition between RNA-binding proteins for the regulation of p21 translation determines cell fate... - Epidermal growth factor receptor stimulation activates the RNA binding protein CUG-BP1 and increases expression of C/EBPbeta-LIP in mammary epithelial cellsBrenda R Baldwin
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
Mol Cell Biol 24:3682-91. 2004..CUG-BP1 is thus a previously unidentified downstream target of EGFR signaling and represents a new translational regulator of LIP expression in human mammary epithelial cells... - Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activityGuo-Li Wang
Huffington Center on Aging and Department of Pathology, and Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
Genes Dev 18:912-25. 2004..These data provide a molecular basis for the development of liver tumors in which the activation of PI3K/Akt pathway neutralizes C/EBPalpha growth inhibitory activity... - Dephosphorylated C/EBPalpha accelerates cell proliferation through sequestering retinoblastoma proteinGuo Li Wang
Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Mol Cell Biol 25:1325-38. 2005..Our data demonstrate a new pathway by which the phosphorylation-dependent switch of biological functions of C/EBPalpha promotes liver proliferation... - RNA CUG-binding protein 1 increases translation of 20-kDa isoform of CCAAT/enhancer-binding protein beta by interacting with the alpha and beta subunits of eukaryotic initiation translation factor 2Nikolai A Timchenko
Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 280:20549-57. 2005..Our data support the hypothesis that CUGBP1 increases translation of LIP by the interaction with the eIF2alpha subunit. This facilitates subsequent recruitment of larger numbers of ribosomes to initiate translation of LIP... - Differential regulation of cyclins D1 and D3 in hepatocyte proliferationDavid G Rickheim
Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA
Hepatology 36:30-8. 2002.... - The leukemic fusion gene AML1-MDS1-EVI1 suppresses CEBPA in acute myeloid leukemia by activation of CalreticulinDaniel Helbling
Institute of Medical Oncology, University Hospital, CH-3010 Bern, Switzerland
Proc Natl Acad Sci U S A 101:13312-7. 2004..These results identify CEBPA as a key target of the leukemic fusion protein AME and suggest that modulation of CEBPA by CRT may represent a mechanism involved in the differentiation block in AME leukemias... - Dynamic assembly of chromatin complexes during cellular senescence: implications for the growth arrest of human melanocytic neviDebdutta Bandyopadhyay
Department of Dermatology, and Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA
Aging Cell 6:577-91. 2007..These results provide new insights into the role of the RB pathway in regulating cellular senescence and implicate HDAC1 as a likely mediator of early chromatin remodeling events... - A novel mechanism of alternative promoter and splicing regulates the epitope generation of tumor antigen CML66-LYan Yan
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
J Immunol 172:651-60. 2004..Our studies have identified the alternative promoter in combination with alternative splicing as a novel mechanism for regulation of the epitope generation of a self-tumor Ag... - CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activitiesYoung Jin Lee
Dept of Laboratory Medicine, Box 0134, 513 Parnassus Ave, San Francisco, CA 94143, USA
Blood 108:2416-9. 2006..We also show that forced expression of C/EBPalpha or C/EBPepsilon in combination with ATRA treatment has a synergistic effect on survival of leukemic mice compared with either therapy alone... - Dynamic regulation of the human dopachrome tautomerase promoter by MITF, ER-alpha and chromatin remodelers during proliferation and senescence of human melanocytesDenise J Schwahn
Departmentsof Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Pigment Cell Res 18:203-13. 2005..We conclude that senescent melanocytes display dramatic changes in the expression of differentiation-related proteins; such changes may in turn result in altered melanocyte function and survival to environmental stresses... - CBFB-SMMHC is correlated with increased calreticulin expression and suppresses the granulocytic differentiation factor CEBPA in AML with inv(16)Daniel Helbling
Department of Clinical Research, University Hospital, Berne, Switzerland
Blood 106:1369-75. 2005..Inhibition of calreticulin by siRNA restored CEBPA levels. Our results suggest that modulation of CEBPA by calreticulin represents a novel mechanism involved in the differentiation block in CBFB-SMMHC AML...
Research Grants
- Regulation of Cell Growth by RNA Binding ProteinsNikolai Timchenko; Fiscal Year: 2007..Together, these studies will provide important insight into how particular RNA binding proteins function through newly discovered pathways to control cell division. ..
- Regulation of Cell Growth by RNA Binding ProteinsNikolai Timchenko; Fiscal Year: 2009..The elucidation of molecular mechanisms of malignant transformations in liver will provide basement for the development of therapeutic approaches to prevent tumors. ..
- C/EBP alpha in Aging LiverNikolai Timchenko; Fiscal Year: 2007..Based on data obtained in this project, we are planning to start developing a strategy to correct liver proliferation in elderly. ..
- MECHANISMS OF C/EBP ALPHA MEDIATED GROWTH ARRESTNikolai Timchenko; Fiscal Year: 2007..C/EBPalpha-S193A knock-in mice will be generated and proliferative capacities of the liver will be examined in these animals. ..
- C/EBP alpha in Aging LiverNikolai Timchenko; Fiscal Year: 2009..Based on data obtained in this project, we are planning to start developing a strategy to correct liver proliferation in elderly. ..
- Molecular mechanisms of C/EBP alpha mediated growth arrestNikolai A Timchenko; Fiscal Year: 2010..The elucidation of these mechanisms will provide basement for the generation of therapeutic approaches to prevent tumors. ..
- Regulation of Cell Growth by RNA Binding ProteinsNikolai A Timchenko; Fiscal Year: 2010..The elucidation of molecular mechanisms of malignant transformations in liver will provide basement for the development of therapeutic approaches to prevent tumors. ..
- Epigenetic Regulation of Cell and Tissue AgingNikolai A Timchenko; Fiscal Year: 2010..If successful, our studies will help define a "histone code for cellular aging";and consequently open new avenues for interventions that target the human epigenome. ..
- MECHANISMS OF C/EBP ALPHA MEDIATED GROWTH ARRESTNikolai Timchenko; Fiscal Year: 2000..In Aim II, liver regeneration will be studied in the p21 knock-out mouse. Finally, Aim III studies will investigate liver regeneration in old rats, which have altered regulation of both C/EBP-alpha and p21. ..
- Mechanisms of C/EBP Alpha Mediated Growth ArrestNikolai Timchenko; Fiscal Year: 2004..Using this biological model, we will test the hypothesis that post-translational modifications of C/EBPa regulate the interaction of C/EBPa with cell cycle proteins. ..
- Molecular mechanisms of C/EBP alpha mediated growth arrestNikolai A Timchenko; Fiscal Year: 2011..The elucidation of these mechanisms will provide basement for the generation of therapeutic approaches to prevent tumors. ..