http://publicationslist.org/data/mikael.altun/atom.xml Mikael Altunhttp://publicationslist.org/mikael.altun$basepathfavicon.icoRecent additions to Mikael Altun's PublicationsList.org pagehttp://publicationslist.org/publications.png2012-10-09T19:20:34Z http://publicationslist.org/mikael.altun/refid20 2012-10-09T19:12:46Z

Bortezomib therapy has proven successful for the treatment of relapsed/refractory, relapsed, and newly diagnosed multiple myeloma (MM); however, dose-limiting toxicities and the development of resistance limit its long-term utility. Here, we show that P5091 is an inhibitor of deubiquitylating enzyme USP7, which induces apoptosis in MM cells resistant to conventional and bortezomib therapies. Bioch...<br/><br/>Dharminder Chauhan, Ze Tian, Benjamin Nicholson, K G Suresh Kumar, Bin Zhou, Ruben Carrasco, Jeffrey L McDermott, Craig A Leach, Mariaterresa Fulcinniti, Matthew P Kodrasov, Joseph Weinstock, William D Kingsbury, Teru Hideshima, Parantu K Shah, Stephane Minvielle, Mikael Altun, Benedikt M Kessler, Robert Orlowski, Paul Richardson, Nikhil Munshi, Kenneth C Anderson (2012) <i>Cancer Cell</i> <i></i> <i></i> 22: 3 345-358<br/>

http://publicationslist.org/mikael.altun/refid17 2012-10-09T19:12:46Z

Background: Synthetic probes that mimic natural substrates can enable the detection of enzymatic activities in a cellular environment. One area where such activity-based probes have been applied is the ubiquitin-proteasome pathway, which is emerging as an important therapeutic target. A family of reagents has been developed that specifically label deubiquitylating enzymes (DUBs) and facilitate cha...<br/><br/>Holger B Kramer, Benjamin Nicholson, Benedikt M Kessler, Mikael Altun (2012) <i>Biochim Biophys Acta</i> <i></i> <i></i> 1823: 11 2029-2037<br/>

http://publicationslist.org/mikael.altun/refid18 2012-07-16T15:08:27Z

Novel ubiquitin-based active site probes including a fluorescent tag have been developed and evaluated. A new, functionalizable electrophilic trap is utilized allowing for late stage diversification of the probe. Attachment of fluorescent dyes allowed direct detection of endogenous deubiquitinating enzyme (DUB) activities in cell extracts by in-gel fluorescence imaging.<br/><br/>Joanna F McGouran, Holger B Kramer, Mukram M Mackeen, Katalin di Gleria, Mikael Altun, Benedikt M Kessler (2012) <i>Org Biomol Chem</i> <i></i> <i></i> 10: 17 3379-3383<br/>

http://publicationslist.org/mikael.altun/refid19 2012-07-16T15:08:27Z

A proper cellular adaptation to low oxygen levels is essential for processes such as development, growth, metabolism, and angiogenesis. The response to decrease in oxygen supply, referred to as hypoxia, is also involved in numerous human diseases including cancer, inflammatory conditions, and vascular disease. The hypoxia-inducible factor 1-α (HIF-1α), a key player in the hypoxic response, is ke...<br/><br/>Mikael Altun, Bin Zhao, Kelly Velasco, Haiyin Liu, Gerco Hassink, Julia Paschke, Teresa Pereira, Kristina Lindsten (2012) <i>J Biol Chem</i> <i></i> <i></i> 287: 3 1962-1969<br/>

http://publicationslist.org/mikael.altun/refid13 2011-11-29T11:43:41Z

Photoactivated cross-linking of peptides to proteins is a useful strategy for identifying enzyme-substrate and protein-protein interactions in cell lysates as demonstrated by studies on the human hypoxia inducible factor system.<br/><br/>Dante Rotili, Mikael Altun, Refaat B Hamed, Christoph Loenarz, Armin Thalhammer, Richard J Hopkinson, Ya-Min Tian, Peter J Ratcliffe, Antonello Mai, Benedikt M Kessler, Christopher J Schofield (2011) <i>Chem Commun (Camb)</i> <i></i> <i></i> 47: 5 1488-1490<br/>

http://publicationslist.org/mikael.altun/refid14 2012-07-16T15:08:27Z

Converting lead compounds into drug candidates is a crucial step in drug development, requiring early assessment of potency, selectivity, and off-target effects. We have utilized activity-based chemical proteomics to determine the potency and selectivity of deubiquitylating enzyme (DUB) inhibitors in cell culture models. Importantly, we characterized the small molecule PR-619 as a broad-range DUB ...<br/><br/>Mikael Altun, Holger B Kramer, Lianne I Willems, Jeffrey L McDermott, Craig A Leach, Seth J Goldenberg, K G Suresh Kumar, Rebecca Konietzny, Roman Fischer, Edward Kogan, Mukram M Mackeen, Joanna McGouran, Svetlana V Khoronenkova, Jason L Parsons, Grigory L Dianov, Benjamin Nicholson, Benedikt M Kessler (2011) <i>Chem Biol</i> <i></i> <i></i> 18: 11 1401-1412<br/>

http://publicationslist.org/mikael.altun/refid15 2011-11-29T11:43:41Z

ABSTRACT: A large quantitative study was carried out to compare the proteome of respiratory syncytial virus (RSV) infected versus uninfected cells in order to determine novel pathways regulated during viral infection. RSV infected and mock-infected HEp2 cells were lysed and proteins separated by preparative isoelectric focussing using offgel fractionation. Following tryptic digestion, purified pep...<br/><br/>Nicola Ternette, Cynthia Wright, Holger B Kramer, Mikael Altun, Benedikt M Kessler (2011) <i>Virol J</i> <i></i> <i></i> 8: 1 <br/>

http://publicationslist.org/mikael.altun/refid16 2011-11-29T11:43:41Z

2-oxoglutarate (2-OG)-dependent oxygenases have diverse roles in human biology. The inhibition of several 2-OG oxygenases is being targeted for therapeutic intervention, including for cancer, anemia, and ischemic diseases. We report a small-molecule probe for 2-OG oxygenases that employs a hydroxyquinoline template coupled to a photoactivable crosslinking group and an affinity-purification tag. Fo...<br/><br/>Dante Rotili, Mikael Altun, Akane Kawamura, Alexander Wolf, Roman Fischer, Ivanhoe K H Leung, Mukram M Mackeen, Ya-Min Tian, Peter J Ratcliffe, Antonello Mai, Benedikt M Kessler, Christopher J Schofield (2011) <i>Chem Biol</i> <i></i> <i></i> 18: 5 642-654<br/>

http://publicationslist.org/mikael.altun/refid10 2011-11-29T11:43:41Z

Microbial pathogens exploit the ubiquitin system to facilitate infection and manipulate the immune responses of the host. In this study, susceptibility to Yersinia enterocolitica and Yersinia pseudotuberculosis invasion was found to be increased upon overexpression of the deubiquitinating enzyme otubain 1 (OTUB1), a member of the ovarian tumour domain-containing protein family. Conversely, OTUB1 k...<br/><br/>Mariola J Edelmann, Holger B Kramer, Mikael Altun, Benedikt M Kessler (2010) <i>FEBS J</i> <i></i> <i></i> 277: 11 2515-2530<br/>

http://publicationslist.org/mikael.altun/refid12 2011-11-29T11:43:41Z

Among the hallmarks of aged organisms are an accumulation of misfolded proteins and a reduction in skeletal muscle mass ("sarcopenia"). We have examined the effects of aging and dietary restriction (which retards many age-related changes) on components of the ubiquitin proteasome system (UPS) in muscle. The hindlimb muscles of aged (30 months old) rats showed a marked loss of muscle mass and conta...<br/><br/>Mikael Altun, Henrike C Besche, Herman S Overkleeft, Rosanna Piccirillo, Mariola J Edelmann, Benedikt M Kessler, Alfred L Goldberg, Brun Ulfhake (2010) <i>J Biol Chem</i> <i></i> <i></i> 285: 51 39597-39608<br/>

http://publicationslist.org/mikael.altun/refid8 2010-10-06T13:20:00Z

OTUB (otubain) 1 is a human deubiquitinating enzyme that is implicated in mediating lymphocyte antigen responsiveness, but whose molecular function is generally not well defined. A structural analysis of OTUB1 shows differences in accessibility to the active site and in surface properties of the substrate-binding regions when compared with its close homologue, OTUB2, suggesting variations in regul...<br/><br/>Mariola J Edelmann, Alexander Iphöfer, Masato Akutsu, Mikael Altun, Katalin di Gleria, Holger B Kramer, Edda Fiebiger, Sirano Dhe-Paganon, Benedikt M Kessler (2009) <i>Biochem J</i> <i></i> <i></i> 418: 2 379-390<br/>

http://publicationslist.org/mikael.altun/refid11 2010-10-06T13:20:00Z

Ubiquitination regulates membrane events such as endocytosis, membrane trafficking and endoplasmic-reticulum-associated degradation (ERAD). Although the involvement of membrane-associated ubiquitin-conjugating enzymes and ligases in these processes is well documented, their regulation by ubiquitin deconjugases is less well understood. By screening a database of human deubiquitinating enzymes (DUBs...<br/><br/>Gerco C Hassink, Bin Zhao, Ramakrishna Sompallae, Mikael Altun, Stefano Gastaldello, Nikolay V Zinin, Maria G Masucci, Kristina Lindsten (2009) <i>EMBO Rep</i> <i></i> <i></i> 10: 7 755-761<br/>

http://publicationslist.org/mikael.altun/refid9 2008-11-04T20:44:15Z

Several disturbances occurring during aging of humans and rodents alike stem from changes in sensory and motor functions. Using a battery of behavioral tests we have studied alterations in performance with advancing age in female and male rats of some frequently used strains. In parallel, we collected survival and body weight data. The median survival age was similar for female and male Sprague-Da...<br/><br/>Mikael Altun, Esbjörn Bergman, Erik Edström, Hans Johnson, Brun Ulfhake (2007) <i>Physiol Behav</i> <i></i> <i></i> 92: 5 911-923<br/>

http://publicationslist.org/mikael.altun/refid2 2007-07-05T11:30:34Z

Loss of skeletal muscle mass (sarcopenia) is a major contributor to disability in old age. We used two-dimensional gel electrophoresis and mass spectrometry to screen for changes in proteins, and cDNA profiling to assess transcriptional regulations in the gastrocnemius muscle of adult (4 months) and aged (30 months) male Sprague-Dawley rats. Thirty-five proteins were differentially expressed in ag...<br/><br/> Altun, Edström, Spooner, Flores-Moralez, Bergman, Tollet-Egnell, Norstedt, Kessler, Ulfhake (2007) <i>Muscle Nerve</i> <i></i> <i></i> : <br/>

http://publicationslist.org/mikael.altun/refid1 2007-07-05T11:30:34Z

Motor disturbances and wasting of skeletal muscles (sarcopenia) causes significant impairment of daily life activities and is a major underlying cause for hospitalization in senescence. Herein we review data and present new findings on aging-specific changes in motoneurons, skeletal muscle and the interplay between motoneurons and target muscle fibers. Although many of the changes occurring during...<br/><br/> Edström, Altun, Bergman, Johnson, Kullberg, Ramírez-León, Ulfhake (2007) <i>Physiol Behav</i> <i></i> <i></i> : <br/>

http://publicationslist.org/mikael.altun/refid3 2007-07-05T11:30:34Z

Muscle atrophy in many conditions share a common mechanism in the upregulation of the muscle-specific ubiquitin E3-ligases atrophy gene-1/muscle atrophy F-box (Atrogin-1/MAFbx) and muscle ring-finger protein 1 (MuRF1). E3-ligases are part of the ubiquitin proteasome pathway utilized for protein degradation during muscle atrophy. In this study, we provide new data to show that this is not the case ...<br/><br/>Erik Edström, Mikael Altun, Martin Hägglund, Brun Ulfhake (2006) <i>J Gerontol A Biol Sci Med Sci</i> <i></i> <i></i> 61: 7 663-674<br/>

http://publicationslist.org/mikael.altun/refid4 2007-07-05T11:30:34Z

Multiple myeloma is a B-cell malignancy for which no curative therapies exist to date, despite enormous research efforts. The remarkable activity of the proteasome inhibitor bortezomib (PS-341, Velcade) observed in clinical trials of patients with relapsed refractory myeloma has led to investigations of the role of the ubiquitin-proteasome pathway in the pathogenesis of myeloma. Here we report a b...<br/><br/>Mikael Altun, Paul J Galardy, Reshma Shringarpure, Teru Hideshima, Richard LeBlanc, Kenneth C Anderson, Hidde L Ploegh, Benedikt M Kessler (2005) <i>Cancer Res</i> <i></i> <i></i> 65: 17 7896-7901<br/>

http://publicationslist.org/mikael.altun/refid5 2007-07-05T11:33:53Z

The Shc family of proteins participates in mitogenic and survival signalling through binding to receptor tyrosine kinases. We report here on the expression of Shc in forebrain, spinal cord and hind limb muscles from 30-month-old rats with different degrees of sensorimotor impairment. ShcA (mRNA and protein) is up-regulated in skeletal muscles and spinal cord of aged rats, and this change relates t...<br/><br/>Xiaogang Jiang, Erik Edstrom, Mikael Altun, Brun Ulfhake (2003) <i>Aging Cell</i> 2: 1 47-57<br/>

http://publicationslist.org/mikael.altun/refid7 2007-07-05T11:34:19Z

In this study we have used fluorescent microspheres to retrogradely label primary sensory neurons in dorsal root ganglia (DRGs). Following injection into peripheral nerves, the animals were allowed to survive up to 480 days. Simple profile count indicates that there is a substantial retention of the labeling still after at least 480 days, i.e. about two-thirds of a rat's life span. Moreover, the a...<br/><br/>M Altun, E Bergman, B Ulfhake (2001) <i>J Neurosci Methods</i> <i></i> <i></i> 108: 1 19-24<br/>

http://publicationslist.org/mikael.altun/refid6 2007-07-05T11:34:19Z

BACKGROUND: The 26S proteasome is responsible for most cytosolic proteolysis, and is an important protease in major histocompatibility complex class I-mediated antigen presentation. Constitutively expressed proteasomes from mammalian sources possess three distinct catalytically active species, beta1, beta2 and beta5, which are replaced in the gamma-interferon-inducible immunoproteasome by a differ...<br/><br/>B M Kessler, D Tortorella, M Altun, A F Kisselev, E Fiebiger, B G Hekking, H L Ploegh, H S Overkleeft (2001) <i>Chem Biol</i> <i></i> <i></i> 8: 9 913-929<br/>