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Articles 1 - 6 of 6

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Suppression Of P53-Dependent Senescence By The Jnk Signal Transduction Pathway, Madhumita Das, Feng Jiang, Hayla Karen Sluss, Chao Zhang, Kevan M. Shokat, Richard A. Flavell, Roger J. Davis Oct 2007

Suppression Of P53-Dependent Senescence By The Jnk Signal Transduction Pathway, Madhumita Das, Feng Jiang, Hayla Karen Sluss, Chao Zhang, Kevan M. Shokat, Richard A. Flavell, Roger J. Davis

Open Access Articles

The JNK signaling pathway is implicated in the regulation of the AP1 transcription factor and cell proliferation. Here, we examine the role of JNK by using conditional and chemical genetic alleles of the ubiquitously expressed murine genes that encode the isoforms JNK1 and JNK2. Our analysis demonstrates that JNK is not essential for proliferation. However, JNK is required for expression of the cJun and JunD components of the AP1 transcription factor, and JNK-deficient cells exhibit early p53-dependent senescence. These data demonstrate that JNK can act as a negative regulator of the p53 tumor suppressor.


C-Jun N-Terminal Kinase 1 Is Required For Toll-Like Receptor 1 Gene Expression In Macrophages, Hooman Izadi, Amirreza T. Motameni, Tonya C. Bates, Elias R. Olivera, Vega Villar-Suarez, Ila Joshi, Renu Garg, Barbara A. Osborne, Roger J. Davis, Mercedes Rincon, Juan Anguita Oct 2007

C-Jun N-Terminal Kinase 1 Is Required For Toll-Like Receptor 1 Gene Expression In Macrophages, Hooman Izadi, Amirreza T. Motameni, Tonya C. Bates, Elias R. Olivera, Vega Villar-Suarez, Ila Joshi, Renu Garg, Barbara A. Osborne, Roger J. Davis, Mercedes Rincon, Juan Anguita

Davis Lab Publications

The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM(3)CSK(4). JNK1, but not JNK2, activity regulates the expression of ...


Requirement Of Jip Scaffold Proteins For Nmda-Mediated Signal Transduction, Norman J. Kennedy, Gilles Martin, Anka G. Ehrhardt, Julie Cavanagh-Kyros, Chia-Yi Kuan, Pasko Rakic, Richard A. Flavell, Steven N. Treistman, Roger J. Davis Sep 2007

Requirement Of Jip Scaffold Proteins For Nmda-Mediated Signal Transduction, Norman J. Kennedy, Gilles Martin, Anka G. Ehrhardt, Julie Cavanagh-Kyros, Chia-Yi Kuan, Pasko Rakic, Richard A. Flavell, Steven N. Treistman, Roger J. Davis

Davis Lab Publications

JIP scaffold proteins are implicated in the regulation of protein kinase signal transduction pathways. To test the physiological role of these scaffold proteins, we examined the phenotype of compound mutant mice that lack expression of JIP proteins. These mice were found to exhibit severe defects in N-methyl-D-aspartic acid (NMDA) receptor function, including decreased NMDA-evoked current amplitude, cytoplasmic Ca(++), and gene expression. The decreased NMDA receptor activity in JIP-deficient neurons is associated with reduced tyrosine phosphorylation of NR2 subunits of the NMDA receptor. JIP complexes interact with the SH2 domain of cFyn and may therefore promote tyrosine phosphorylation and activity of ...


Structural Insights Into The Interaction Of The Evolutionarily Conserved Zpr1 Domain Tandem With Eukaryotic Ef1a, Receptors, And Smn Complexes, Ashwini K. Mishra, Laxman Gangwani, Roger J. Davis, David G. Lambright Aug 2007

Structural Insights Into The Interaction Of The Evolutionarily Conserved Zpr1 Domain Tandem With Eukaryotic Ef1a, Receptors, And Smn Complexes, Ashwini K. Mishra, Laxman Gangwani, Roger J. Davis, David G. Lambright

Open Access Articles

Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded beta helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the ...


Direct Comparison Of Feature Tracking And Autocorrelation For Velocity Estimation, Gregory R. Bashford, Derek J. Robinson Apr 2007

Direct Comparison Of Feature Tracking And Autocorrelation For Velocity Estimation, Gregory R. Bashford, Derek J. Robinson

Biomedical Imaging and Biosignal Analysis Laboratory

Feature tracking is an algorithm for estimating tissue motion and blood flow using pulse-echo ultrasound. It was proposed as a computationally simpler alternative to other techniques such as autocorrelation and time-domain cross correlation. The advantage of feature tracking is that it selectively extracts easily identifiable parts of the speckle signal (e.g., the local maxima), reducing the amount of information being processed. Studies on feature tracking to date have used stationary, specklegenerating targets to simulate blood flow. Also, feature tracking has not been compared with accepted commercial methods. This study directly compares feature tracking performance with the complex autocorrelation method ...


A Proposal For Robust Temperature Compensation Of Circadian Rhythms, Christian I. Hong, Emery D. Conrad, John J. Tyson Jan 2007

A Proposal For Robust Temperature Compensation Of Circadian Rhythms, Christian I. Hong, Emery D. Conrad, John J. Tyson

Open Dartmouth: Faculty Open Access Scholarship

The internal circadian rhythms of cells and organisms coordinate their physiological properties to the prevailing 24-h cycle of light and dark on earth. The mechanisms generating circadian rhythms have four defining characteristics: they oscillate endogenously with period close to 24 h, entrain to external signals, suffer phase shifts by aberrant pulses of light or temperature, and compensate for changes in temperature over a range of 10°C or more. Most theoretical descriptions of circadian rhythms propose that the underlying mechanism generates a stable limit cycle oscillation (in constant darkness or dim light), because limit cycles quite naturally possess the first ...