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Articles 1 - 7 of 7

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

The Cjun Nh2-Terminal Kinase (Jnk) Signaling Pathway Promotes Genome Stability And Prevents Tumor Initiation, Nomeda A. Girnius, Yvonne J. K. Edwards, David S. Garlick, Roger J. Davis Jun 2018

The Cjun Nh2-Terminal Kinase (Jnk) Signaling Pathway Promotes Genome Stability And Prevents Tumor Initiation, Nomeda A. Girnius, Yvonne J. K. Edwards, David S. Garlick, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

Breast cancer is the most commonly diagnosed malignancy in women. Analysis of breast cancer genomic DNA indicates frequent loss-of-function mutations in components of the cJUN NH2-terminal kinase (JNK) signaling pathway. Since JNK signaling can promote cell proliferation by activating the AP1 transcription factor, this apparent association of reduced JNK signaling with tumor development was unexpected. We examined the effect of JNK deficiency in the murine breast epithelium. Loss of JNK signaling caused genomic instability and the development of breast cancer. Moreover, JNK deficiency caused widespread early neoplasia and rapid tumor formation in a murine model of breast cancer. This tumor ...


An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis Sep 2016

An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis Aug 2016

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab Publications

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis Feb 2016

Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis

Davis Lab Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is implicated in the response to metabolic stress. Indeed, it is established that the ubiquitously expressed JNK1 and JNK2 isoforms regulate energy expenditure and insulin resistance. However, the role of the neuron-specific isoform JNK3 is unclear. Here we demonstrate that JNK3 deficiency causes hyperphagia selectively in high fat diet (HFD)-fed mice. JNK3 deficiency in neurons that express the leptin receptor LEPRb was sufficient to cause HFD-dependent hyperphagia. Studies of sub-groups of leptin-responsive neurons demonstrated that JNK3 deficiency in AgRP neurons, but not POMC neurons, was sufficient to cause the hyperphagic response. These ...


Determination Of Fatty Acid Oxidation And Lipogenesis In Mouse Primary Hepatocytes, Thomas E. Akie, Marcus P. Cooper Aug 2015

Determination Of Fatty Acid Oxidation And Lipogenesis In Mouse Primary Hepatocytes, Thomas E. Akie, Marcus P. Cooper

GSBS Student Publications

Lipid metabolism in liver is complex. In addition to importing and exporting lipid via lipoproteins, hepatocytes can oxidize lipid via fatty acid oxidation, or alternatively, synthesize new lipid via de novo lipogenesis. The net sum of these pathways is dictated by a number of factors, which in certain disease states leads to fatty liver disease. Excess hepatic lipid accumulation is associated with whole body insulin resistance and coronary heart disease. Tools to study lipid metabolism in hepatocytes are useful to understand the role of hepatic lipid metabolism in certain metabolic disorders. In the liver, hepatocytes regulate the breakdown and synthesis ...


Impact Of Collateral Enlargement On Smooth Muscle Phenotype, Alexander Jerome Bynum Dec 2011

Impact Of Collateral Enlargement On Smooth Muscle Phenotype, Alexander Jerome Bynum

Master's Theses and Project Reports

Peripheral Artery Disease is a very serious disease characterized by an arterial occlusion due to atherosclerotic plaques. In response to an arterial occlusion, arteriogenesis occurs, causing smooth muscle cells to transition from a contractile to synthetic state. Also following an arterial occlusion, functional impairment was seen in the collateral circuit. An immunofluorescence protocol was developed in order to assess the impact of collateral enlargement (arteriogenesis) on smooth muscle phenotype at various time points. Smooth muscle α-actin was used to mark all smooth muscle cells, Ki-67 was used to label proliferating smooth muscle cells, and a fluorescent nuclear stain was used ...


Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger Apr 2008

Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger

Davis Lab Publications

Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss ...