Study Examines How Rheumatoid Arthritis Destroys Bone Aug 26, 2008
In experiments with mice, the University of Rochester team found that TNF alpha affects osteoblasts through an enzyme called Smad Ubiquitin Regulatory Factor 1 (Smurf1) which, in turn, turns off two proteins that drive bone-building. "The significance of our study is that it identifies Smurf1 as the signaling partner through which TNF does its damage in RA-related bone loss," Lianping Xing, assistant professor of pathology and laboratory medicine, said in a university news release. (MEDLINEplus)
Researchers discover how rheumatoid arthritis causes bone loss Aug 21, 2008
The current study provides the first direct proof that the TNF alpha affects osteoblasts through an enzyme called Smad Ubiquitin Regulatory Factor 1 (Smurf1), which in turn shuts down two proteins that would otherwise drive bone-building ... D., at Stony Brook University in New York discovered that Smurf1 helps to attach a protein tag called ubiquitin to aging proteins in need of disposal ... Genetically engineered mice with the Smurf1 gene removed no longer responded to TNF alpha because Smurf1... (EurekAlert!)
Model For Neurological Disorder 'Angelman Syndrome' Developed Aug 16, 2008
The UBE3A protein is an enzyme that attaches a small protein called ubiquitin to other proteins. Ubiquitin attachment signals that the tagged protein needs to be degraded. (Science Daily)
'Cellular rubbish' may hold key to ageing process Aug 12, 2008
There are two major cleaning systems in the cells, one that depends on the proteasome, a cylindrical enzyme made up of many protein components that acts like a salami slicer to cut abnormal protein molecules labelled for disposal by a molecule called ubiquitin ... "To our surprise we found that in animals that we repair the lysosomal pathway (as we did in this work), when we look at the ubiquitin/proteasome system it also seems to work better.". (Telegraph.co.uk)
Water Is 'Designer Fluid' That Helps Proteins Change Shape Aug 7, 2008
In tests on ubiquitin, a common protein in cells, the researchers found that water molecules bound to the protein changed to a native-type arrangement much faster than the protein. The water motion helped establish the correct configuration, making it much easier for the protein to fold. (Science Daily)
Death, Division Or Cancer? Newly Discovered Checkpoint Process Holds The Line In Cell Division Jul 5, 2008
D., of Technion, discovered the ability of MCF2 to block mitosis by shutting down an ubiquitin ligase enzyme known as the anaphase-promoting complex/cyclosome (APC/C) ... D., for the discovery of ubiquitin-mediated protein degradation at Fox Chase. (Science Daily)
Refusal Of Suicide Order: Why Tumor Cells Become Resistant Jun 25, 2008
Winter et al. Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nature Cell Biology, 2008; DOI. Adapted from materials provided by , via , a service of AAAS.. (Science Daily)
'PLoS ONE' STUDY: A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice Jun 4, 2008
Only four GO terms were impacted by both CR and resveratrol across all tissues (), and these were chromatin assembly or disassembly (GO:0006333), regulation of transcription from RNA Polymerase II promoter (GO:0006357), transcription from RNA polymerse II promoter (GO:0006366), and ubiquitin cycle (GO:0006512). Analysis of individual genes within these classes suggests that both CR and resveratrol have a major impact on expression of genes that play important roles in chromatin remodeling that... (USA Today -- Tech)
New Target For Cancer Drugs? Gatekeepers Are Discovered In The Human Cell 'Shredder' May 28, 2008
Biochemist report finding a long-awaited receptor for ubiquitin on the proteasome which may have a key role in fighting tumors ... In the current edition of the scientific journal "Nature" they report finding the long-awaited receptor for ubiquitin on the proteasome ... However, Koraljka Husnjak, a postdoctoral researcher found a way to isolate the ubiquitin binding domain in the mammalian protein, that was amenable for rapid crystallization and subsequent determination of its structure. (Science Daily)
A Protein's Role In Enabling AIDS Virus To Reproduce Detailed May 28, 2008
Thus, the team revealed for the first time not only that Vpx interacted with this system -- called the ubiquitin-dependent proteosomal protein degradation mechanism -- but also identified precisely the way it does so, via a series of intermediate steps ... Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for Cullin 4 E3 ubiquitin ligase to enable macrophage infection. (Science Daily)
How Arsenic Can Cure One Type Of Leukemia Apr 20, 2008
The work of the French team, like that of an English team publishing in the same journal, shows that RNF4 binds to PML-SUMO or PML/RARA-SUMO. It then fixes another peptide, ubiquitin, onto this complex. Ubiquitin is known to lead to the degradation of proteins to which is binds ... Ubiquitin then modifies the PML/RARA-SUMO protein. (Science Daily)
New Insights Into Cellular Death And The Aging Process Apr 18, 2008
31, 2003) Researchers at the University of California, San Diego (UCSD) School of Medicine have identified a previously unknown component of the body's cellular garbage disposal called the ubiquitin. (Mar. (Science Daily)
RING Finger Protein 5 May Guide Treatment For Muscle Disease In Older Adults Apr 8, 2008
Ubiquitin ligase RNF5 (or RING Finger Protein 5) acts much like one of these quality-control inspectors at the end of the assembly line by tagging defective protein products so that they can be recycled ... We know the substrates for this ubiquitin ligase in C. elegans, but not yet in human muscle. (Science Daily)
Protein Inhibits Ebola From Reaching Out To Infect Neighboring Cells Mar 7, 2008
VP40 buds from mammalian cells independent of other viral proteins, and efficient release of VP40 virus-like particles, VLPs, requires interactions with host proteins such as tsg101 and Nedd4, an E3 ubiquitin ligase. Ubiquitin itself is thought to be exploited by Ebola virus to facilitate efficient virus egress ... Addressing the molecular mechanism of this inhibition, the researchers demonstrated that ISG15 interacts with Nedd4 ubiquitin ligase and inhibits ubiquitination of VP40, thus blocking... (Science Daily)
Adult-Onset Obesity Seen In Mice When Gene Disrupted Feb 29, 2008
28, 2008) Texas and California scientists who disrupted one type of the gene ubiquitin (Ubb) in mice observed neuronal death in the hypothalamus, impaired control of energy balance and adult-onset obesity in the rodents ... Ubiquitin is a small protein in the cell that marks unwanted proteins for destruction, said research co-author Xin-Yun Lu, Ph ... This study shows that the deletion of a ubiquitin gene, Ubb, caused neurodegeneration in the hypothalamus, an important brain area for maintaining... (Science Daily)
Deadly Virus Strips Away Immune System's Defensive Measures Dec 14, 2007
Those same knives also cut the bonds between cellular proteins and ubiquitin, another protein related to ISG15 that is key for bodily defense against viruses ... Frias-Staheli N, Giannakopoulos NV, Kikkert M, Taylor SL, Bridgen A, Paragas JJ, Richt JA, Rowland RR, Schmaljohn CS, Lenschow DJ, Snijder EJ, Garcia-Sastre A, Virgin HW IV. Ovarian tumor-domain containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. (Science Daily)
Novel Mechanism For Spread Of Sarcoma Tumors Discovered Nov 30, 2007
Weissman, Khanna, and colleagues started with a protein known as gp78, which tags specific proteins with ubiquitin ... The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. (Science Daily)
Key To Unlocking The Secret Of Highly Specific DNAzyme Catalysis Discovered Nov 14, 2007
25, 2007) The cell labels the proteins it wants to dispose with Ubiquitin (Ub). Malfunctions in the ubiquitin-proteasome system can be fatal for the organism, resulting in cancer and immunological disorders. (Science Daily)
Atrogin Breaks Down The Side Effects Of Statins Nov 13, 2007
Article: The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity, Journal of Clinical Investigation. Adapted from materials provided by. (Science Daily)
Gene Expression Profiling Of Dengue Virus Infection In Cell Lines And Patients Nov 11, 2007
From the activated genes, the researchers identified three pathways common to in vitro and in vivo infection; the NF-kappaB initiated immune pathway, the type I interferon pathway, and the ubiquitin proteasome pathway. They next found that inhibiting the ubiquitin proteasome pathway, or activating the type I interferon pathway, resulted in significant inhibition of viral replication whereas inhibiting the NF-kappaB initiated immune pathway had no effect on viral replication. (Science Daily)
Protein SENP1 Could Be New Target For Cancer Therapies Nov 6, 2007
The scientists discovered what they dubbed Sentrin and later named SUMO (Small Ubiquitin-related Modifier) proteins ... Because they attach to many proteins and alter them, they resemble the well-known ubiquitin proteins which, by linking to proteins, target them for eventual break-down ... That led them to another, surprising finding - that if SENP1 does not clip off SUMO from SUMO-modified HIF1a when it is inside the nucleus, that SUMO then acts like ubiquitin, targeting destruction of HIF1a. (Science Daily)
Advances In Drug Screening: Building A Better Haystack For The Needles Of Tomorrow Oct 26, 2007
Identification of inhibitors for MDM2 ubiquitin ligase activity from natural products by a novel high throughput electrochemiluminescent screen. Scientists laboring intensively to develop new therapeutics often turn to naturally produced molecules used by plants or microrganisms to ward off predators. (Science Daily)
New cell death pathway involved in sperm development Sep 18, 2007
This process eventually pointed them to three distinct genes that encode different protein components of a complex called Cullin-3 ubiquitin ligase. Cullins are members of the E3 ubiquitin ligase family, which label other proteins with ubiquitin, a molecule that marks them for degradation ... Before this study, only IAPs, another class of E3 ubiquitin ligases, had been identified as caspase regulators. (EurekAlert!)
How To Enhance Muscle Function Sep 13, 2007
Furthermore, in slow fibers, class II HDACs were degraded by the ubiquitin proteasome system such that slow fiber identity was maintained. In the second study, Shin'ichi Takeda and colleagues from the National Center of Neurology and Psychiatry, Tokyo, showed that in mice, one mechanism by which tail suspension causes muscle atrophy is that it alters the function of a protein known as nNOS, which leads to the activation of Foxo3a, which, in turn, upregulates the expression of various... (Science Daily)
A New Understanding of Mechanisms That Trigger Cancer Cell Growth Aug 11, 2007
In a cell's interior, the function of the ubiquitin molecule is to "clean house." It attaches itself to proteins that must disappear and triggers their degradation; in doing so, it allows a number of mechanisms to be minutely controlled. This new study reveals that ubiquitin also promotes interactions between proteins known as Cb-b ... However, in some cancer patients this mitigation mechanism does not appear to function, partly because the ubiquitin does not attach itself correctly to the cell... (Science Daily)
Gene-transcription machinery seen poised for action, held in check until needed Jul 26, 2007
In their investigations, the scientists were able to identify a single molecule called ubiquitin that, when in place, appears to be able to pause the transcription process after the needed machinery has been assembled ... At the appropriate time, ubiquitin is removed, and this triggers polymerase action ... In earlier work, Berger and her coworkers looked at ways in which the addition and removal of a small protein called ubiquitin modified particular histones to regulate gene expression. (EurekAlert!)
Major breakthrough in understanding how HIV interferes with infected cell division Jul 13, 2007
This protein complex, designated DDB1-CUL4-VprBP, is involved in a process called ubiquitination. Ubiquitination is a mechanism by which a small protein called ubiquitin is conjugated to cellular proteins in order to modulate their biological activity or induce their degradation ... The researchers demonstrated that association of Vpr with this ubiquitinating complex, also called an E3 ubiquitin ligase complex, is essential for the defect in cell division induced by Vpr. (EurekAlert!)
Clocking In And Out Of Gene Expression Jun 16, 2007
" In studies of breast cancer cells, O'Malley and his colleagues showed how the clock works. Using steroid receptor coactivator-3 (SRC-3), they demonstrated that activation requires addition of a phosphate molecule to the protein at one spot and addition of an ubiquitin molecule at another point. Each time the message of the gene is transcribed into a protein, another ubiquitin molecule is chained on. Five ubiquitins in the chain and the protein is automatically destroyed. "It's built-in self... (Science Daily)
Scientists Link Cell's Protein Recycling Systems Jun 15, 2007
The ubiquitin-proteasome pathway marks unwanted proteins with ubiquitin tags and shuttles them for rapid breakdown to a complicated structure called the proteasome ... In the process of screening, our attention was drawn to HDAC6 because we already knew that it could bind to ubiquitin-tagged proteins and transport them within the cell. (Science Daily)
Possible New Breast Cancer Gene Discovered May 28, 2007
More specifically, modification of proteins in the cell nucleus -- by another protein called ubiquitin -- that are tightly bound to DNA are responsible for signaling BRCA1 via Rap80 to action. Rap80 binds to specific types of ubiquitin that concentrate at DNA damage sites, enabling BRCA1 to be recruited to sites of damage. (Science Daily)
New impetus through networking May 12, 2007
The role of ubiquitin-like protein modifications (UbF) in cells will be investigated in a project called "The Regulatory and Functional Network of Ubiquitin Family Proteins". The UbF and network properties that have been discovered in recent years provide the main focus of this project. (EurekAlert! -- Business News)
Discovery in plants suggests entirely new approach to treating human cancers Apr 5, 2007
Until now it was believed enzymes like TIR1, called ubiquitin ligases, could only be controlled through protein-protein interactions. Ubiquitin ligases influence growth and light response in plants, poison mitigation in yeasts and also cancerous cell division in humans ... "Although ubiquitin ligases have long been recognized as potential drug targets for treating cancers and other human diseases, it's been a bumpy road for scientists to come up with a feasible approach," said University of... (EurekAlert!)
Early Defense Mechanism Resists Pseudomonas Aeruginosa Infection In Mice Jan 20, 2007
Reference: The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T--mediated virulence (). Note: This story has been adapted from a news release issued by Journal Of Clinical Investigation. (Science Daily)
Novel regulation of the common tumor suppressor PTEN Jan 12, 2007
Researchers found that NEDD4-1 is a key component in eliminating PTEN from cells by adding a molecular tag, ubiquitin, to PTEN causing degradation in the cellular machinery called proteasome ... The second study by Dr. Pier Paolo Pandolfi of Memorial Sloan-Kettering and colleagues found that the ubiquitination of PTEN by NEDD4-1 also regulates another important aspect of PTEN, its cellular localization ... The Pandolfi and Jiang labs showed that the PTEN mutation in these patients prevented the... (EurekAlert!)
Latest Research in Blood Diseases to be Presented at the Annual Meeting of the American Society of Hematology Dec 7, 2006
His lecture will focus on his study of the ubiquitin pathway, which plays an important role in the degradation of cellular proteins, and for which he won a Nobel Prize in 2004. The study of this particular pathway may lead to the development of new treatment modalities, such as treatments for multiple myeloma. (PR Newswire)
An AIDS-related virus tricks cells to become tumors, new Penn study finds Nov 9, 2006
This refers to a pathway in all cells whereby a protein aptly named ubiquitin binds to cellular proteins and marks them for degradation ... Ubiquitylation and degradation involve a complex set of proteins in addition to ubiquitin. (EurekAlert!)
Nobel Prize blurs boundaries Oct 12, 2006
The 2005 prize came after a run of bio-related chemistry prizes: in 2002 for determining the structure of biological macromolecules; in 2003 for deciphering channels in cell membranes; and in 2004 for the discovery of the role of ubiquitin in intracellular protein degradation. "Chemistry is becoming more applied," Schrock suggests as one reason for the trend. (Nature News Service)
MIT Finds Most Complex Protein Knot Ever Seen Sep 28, 2006
MIT researchers recently found that human ubiquitin hydrolase, shown here, has the most complicated knot ever observed in a protein ... Most had a simple three-crossing, or trefoil knot, a few had four crossings, and the most complicated, a five-crossing knot, was initially found in only one protein - ubiquitin hydrolase ... That complex knot may hold some protective value for ubiquitin hydrolase, whose function is to rescue other proteins from being destroyed - a dangerous job. (Science Daily)
Researchers Restore Memory Lost In Mice With Alzheimer's Aug 26, 2006
The research suggests that boosting the function of this enzyme, known as ubiquitin C-terminal hydrolase L1 (Uch-L1), may provide a promising strategy for battling Alzheimer's disease, and perhaps reversing its effects. In the new study, the Columbia researchers discovered that the enzyme Uch-L1 is part of a molecular network that controls a memory molecule called CREB, which is inhibited by amyloid beta proteins in people with Alzheimer's. (Science Daily)
Study reveals how cells destroy faulty proteins in cystic fibrosis Aug 11, 2006
The trash collectors newly identified by the Cyr group are two different ubiquitin ligases, proteins that specifically recognize misshaped regions of CFTR and tag them with a degradation signal known as ubiquitin. The ubiquitin tag tells the cell to destroy the marked CFTR, a process overseen by a destroyer called the proteasome ... This trash system is known as the ubiquitin proteasome pathway. (EurekAlert!)
Health and Science News Roundup Jul 5, 2006
Im Dong-soo and his colleagues at the Korea Research Institute of Bioscience and Biotechnology worked with mice to show that E2-EPF ubiquitin carrier protein triggers metatastic cells, the Korea Times reported Monday. By targeting the protein, which has something to do with cancers in the breast, liver and bowel, we think we will be able to come up with effective drugs in the future,' he said. (Monsters and Critics.com)
Molecular Security Mechanism For Keeping Mutations In Check May 6, 2006
The actual mechanism works with a sort of molecular clamp that holds the DNA copying enzyme onto the strand of DNA. When the enzyme encounters DNA damage, a small molecule called ubiquitin attaches to the clamp. The ubiquitin, in this case, serves to anchor replacement DNA polymerase molecules -- careless ones -- to the clamp ... The p21 then acts as a sort of facilitator, helping to fasten the proper ubiquitin in place and clearing stalled DNA polymerase out of the way so its replacement can... (Science Daily)
New mechanism for essential genome-wide gene silencing identified Apr 15, 2006
The research team also noted a dynamic interplay between the addition of a SUMO protein to a histone sumoylation and the addition of either an acetyl group or a ubiquitin protein to a histone. The processes appear to be mutually exclusive. (EurekAlert!)
Study Describes How Cells Return To Normal After Responding To Stress Apr 4, 2006
But CHIP also has another function -- as an ubiquitin ligase. "Ubiquitin ligases are generally involved in tagging proteins with a signal that allows them to be recognized by the proteasome, which is the major garbage can for proteins in a cell," Patterson said ... "Our model is that CHIP is the protein that is responsible for targeting chaperone substrates for degradation. The thinking is that when a protein is too damaged to be refolded, CHIP ubiquitinates that protein so that it can be... (Science Daily)
New Pathway Could Present An Intervention Point For Cancer Treatment Jan 28, 2006
Other modes of taking proteins to the proteasome for destruction involve adding a molecule called ubiquitin and using energy. "This molecule does not require ubiquitin or an energy source," he said. (Science Daily)
