14,185 research outputs found
Retracted. ERK and the F-box protein betaTRCP target STAT1 for degradation
No full textThis article has been withdrawn by Paul A. Townsend, Richard A. Knight, Sean P. Barry, David S. Latchman, and Anastasis Stephanou. An investigation at University College London determined that a duplicated blot in Fig. 1, A and B, the GAPDH blot is the same, flipped horizontally. The withdrawing authors sincerely apologize to the scientific community for any confusion or adverse consequences resulting from the publication of the article. Original Abstract:The transcription factor STAT1 has roles in development, homeostasis, cellular differentiation, and apoptosis and has been postulated to function as a tumor suppressor. STAT1 is activated by tyrosine or serine phosphorylation in response to specific cytokines or following a variety of stress-induced stimuli. STAT1 activity is carefully regulated to prevent sustained STAT1-mediated transcription, although the molecular mechanisms involved in the modulation of STAT1 stability are poorly understood. Here we show that activated STAT1 is degraded at the proteasome by a mechanism involving the F-box E3 ligase, SCF(betaTRCP). Active p42/p44 MAPK-ERK phosphorylates STAT1 on serine 727 and targets it for proteasomal degradation. SCF(betaTRCP) binds wild-type STAT1 but not the nonphosphorylatable mutant STAT1(S727A). Moreover, silencing betaTRCP expression or pharmacological inhibition of ERK activity stabilized STAT1 expression. These data suggest that constitutively active ERK may inappropriately degrade STAT1, with loss of its pro-apoptotic and tumor suppressor functions
BAG-1: a multi-functional pro-survival molecule
No full textBAG-1 is a multi-functional protein that exists as three functionally distinct and differentially localized isoforms which originate from a single mRNA and interact with a wide range of cellular targets. These include heat shock proteins, nuclear hormone receptors, signalling molecules, the anti-apoptotic BCL-2 protein and components of the ubiquitylation/proteasome machinery. Overexpression of BAG-1 isoforms has been demonstrated to regulate apoptosis, proliferation, transcription, metastasis and cell motility in a wide variety of cell systems. Since BAG-1 has a role in many biological pathways there is increasing evidence supporting the view that BAG-1 is an important molecule in disease, for example, potentially modulating both cell survival and response to nuclear hormones in breast cancer, and BAG-1 is a potential molecular target for therapeutic intervention
Withdrawal: ERK and the F-box protein β TRCP target STAT1 for degradation
No full textThis article has been withdrawn by Paul A. Townsend, Richard A. Knight, Sean P. Barry, David S. Latchman, and Anastasis Stephanou. An investigation at University College London determined that a duplicated blot in Fig. 1, A and B, the GAPDH blot is the same, flipped horizontally. The withdrawing authors sincerely apologize to the scientific community for any confusion or adverse consequences resulting from the publication of the article.</p
Role of the JAK-STAT pathway in myocardial injury
No full textCardiovascular pathologies are an enormous burden in human health and despite the vast amount of research; the molecular mechanisms and pathways that control the underlying pathologies are still not fully appreciated. The Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway has recently been shown to be an integral part of the response of the myocardium to various cardiac insults, including myocardial infarction, oxidative damage, myocarditis, hypertrophy and remodeling, in addition to having a prominent role in cardioprotective therapies such as ischaemic preconditioning. Here, recent advances in the understanding of how the JAK-STAT pathway orchestrates the response to cellular damage in the myocardium are discussed, along with the potential benefits and challenges in manipulating this pathway in cardiovascular therapy
A minimal Bcl-x promoter is activated by Brn-3a and repressed by p53
No full textThe Brn-3a transcription factor stimulates the expression of the anti-apoptotic Bcl-2 and Bcl-x proteins and protects neuronal cells from apoptosis. Here we show that a minimal Bcl-x promoter is activated by Brn-3a and that this stimulation is prevented by the pro-apoptotic p53 protein. Both these effects are mediated via Bcl-x promoter sequences, which are indistinguishable from those required for minimal basal promoter activity. A newly described upstream Bcl-x promoter is also activated by Brn-3a with this activation being prevented by p53. Hence, Brn-3a-mediated activation of two distinct Bcl-x promoters and of the Bcl-2 promoter is blocked by p53 whereas this is not observed for Brn-3a activated promoters derived from genes not involved in inhibiting apoptosis. p53 therefore appears to specifically target the activation by Brn-3a of promoters derived from genes with an anti-apoptotic effect and this may be involved in the pro-apoptotic activity of p53
Newton's Laws
No full textAuthored and curated by David P. Stern, this series of web pages, part of "From Stargazers to Starships," describes Newton's three laws of motion and the two concepts on which they are based, force and inertia. The author breaks down the page in this fashion: the concept of force, motion against outside resistance, and motion with significant resistance. The author also provides additional links for further study on the life of Issac Newton. A lesson plan for instructors is also provided
C.C. Slaughter's Lazy S Ranch in Cochran and Hockley counties, 1898-1921.
No full textLikely added to or created for the author's thesis: "A Cattle Kingdom on Texas' Last Frontier: C. C. Slaughter's Lazy S Ranch" (Texas Tech University, 1970).Scale approximately 1:337,920 (W 102°59'24"--W 102°18'53"/N 33°50'54"--N 33°24'07")The map illustrates the 250,000-acre holdings of C.C. Slaughter, known as the "Cattle King of Texas," before the ranch's liquidation and subdivision beginning in 1921 (following his death in 1919)
STAT3 modulates the DNA damage response pathway
No full textThe STAT3 transcription factor is well known to function as an anti-apoptotic factor, especially in numerous malignancies. Recently we showed that STAT3 is cytoprotective and that cells lacking STAT3 are more sensitive to oxidative stress. A key feature of oxidative stress involves activation of the DNA damage pathway. However, a role for STAT3 or its contribution in response to DNA damage has not been described. In the present study we show that cells lacking STAT3 are less efficient in repairing damaged DNA. Moreover, STAT3 deficient cells show reduced activity of the ATM-Chk2 and ATR-Chk1 pathways, both important pathways in sensing DNA damage. Finally we show that MDC1, a regulator of the ATM-Chk2 pathway and facilitator of the DNA damage response, is modulated by STAT3 at the transcriptional level. These findings demonstrate that STAT3 is necessary for efficient repair of damaged DNA, partly by modulating the ATM-Chk2 and ATR-Chk1 pathways
Dr. David Salisbury – Faculty Author Interview
No full textDavid Salisbury, Assistant Professor of Geography and the Environment, discusses his recent article, “Fronteras Vivas or Dead Ends? The Impact of Military Settlement Projects in the Amazon Borderlands”, in the Journal of Latin American Geography. This article describes a case study in the Peruvian Amazon which explores the natural resource management, household economics, and political geography of a borderland military base and associated settlement
Remembering BC\u27s 1983 Solidarity Uprising — with David Spaner
No full textBio: David Spaner has worked as a feature writer, movie critic, reporter, and editor for numerous newspapers and magazines. David\u27s also been a cultural/political organizer (Yippie, manager of the punk band The Subhumans). He is the author of Dreaming in the Rain and Shoot It! Hollywood, Inc. and the Rising of Independent Film.In 2021, Spaner published a behind-the-scenes book about the Solidarity resistance movement, Solidarity: Canada\u27s Unknown Revolution of 1983 (Ronsdale 2021) documenting the event using intimate storytelling and melding cultural and rebel politics to provide insight into the conflicts that are still with us. It was the largest political protest in the province\u27s history and threatened to end in an all-out general strike. Resources: Solidarity: Canada\u27s Unknown Revolution of 1983 (Ronsdale 2021): https://ronsdalepress.com/all-books/solidarity/SHOOT IT! Hollywood Inc. and the Rising of Independent Film (Arsenal Pulp Press 2012): https://arsenalpulp.com/Books/S/Shoot-ItDreaming in the Rain: How Vancouver Became Hollywood North by Northwest (Arsenal Pulp Press 2002): https://arsenalpulp.com/Books/D/Dreaming-in-the-Rai
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