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All life is regulated by the reversible phosphorylation of proteins. The phosphorylation state of a protein determines its biochemical properties and biological functions and is regulated by the opposing catalytic forces of protein kinases and phosphatases. In this tug-of-war the role of the phosphatases has been neglected for a long time due to the misconception of phosphatases being promiscuous, non-specific enzymes that only set the stage for kinases. The reason for that resided in a lack of knowledge on the complex nature of these enzymes. With the growing knowledge on phosphatases their equal importance for many biological processes became clear. A major phosphoserine/-threonine phosphatase in the cell is protein phosphatase 2A (PP2A). PP2A stands for a large multisubunit holoenzyme family, each of which fulfills its own substrate specific tasks. We are trying to answer how the biogenesis of PP2A holoenzymes is regulated and what the substrates of PP2A holoenzymes are.
We study PP2A biogenesis in yeast and mammals using biochemical, genetic and immunological approaches. Key tools for our analysis are monoclonal antibodies with exquisite specificity. We generated the worldwide first and still unique antibody recognizing the PP2A carboxy-terminal methylation, a modification of the catalytic subunit essential for the assembly of PP2A holoenzymes with tumor-suppressive functions. Our analysis in yeast unraveled some of the basic principles of PP2A biogenesis and laid the foundation to the present PP2A biogenesis model. Despite the high degree of conservation much less is known about this process in higher eukaryotes. We generated a conditional knockout mouse of the PP2A chaperone PTPA and are analyzing the knockout phenotype on a molecular level. Detailed knowledge on mammalian PP2A biogenesis is required for novel therapeutic strategies such as SMAPs, recently developed drugs that restore the tumor-suppressive function of PP2A.
Egon Ogris studied medicine at the University of Vienna and obtained his MD in 1987. From 1992-1995 Egon was a postdoctoral fellow at the Dana-Farber Cancer Institute/Harvard Medical School in Boston. In 1995 he started his own group at the University of Vienna (now Medical University of Vienna), where he habilitated in 2000.
Dr. Bohr-Gasse 9
1030 Vienna
Room: 2.117
+43-1-4277-61730
Two new papers from our lab now show that several antibodies recognizing the enzyme PP2A, and an antibody widely used in a technique called Myc tagging lack the precision for their intended tasks. The findings published in “Science Signaling” show that this and other Myc tag antibodies yield inconsistent results depending on the molecular surrounding of the tag, and that antibodies recognizing PP2A often prove to be unsuitable for measuring the activity of this enzyme.
Read the abstracts:
We have uncovered the function of PTPA as a PP2A activation chaperone. This activation step is coupled to the interaction with the structural PP2A subunit and is under surveillance of the PP2A methylesterase. Methylation of the PP2A catalytic subunit is an essential requirement for the assembly of trimeric holoenzymes.
The transient interaction between PP2A and its substrates cannot be detected by standard methods, which is the major reason for the lack of knowledge on the “true in vivo” substrates of PP2A. In collaboration with the Ammerer lab we developed a protein proximity assay termed M-TRACK, which makes it possible to detect and analyze such short-lived PPIs in vivo.
We generate monoclonal antibodies for research and diagnosis, offer a monoclonal antibody service and develop novel approaches to improve antibody specificity. Examples are antibodies specific for lamin A/C point-mutants to study laminopathies, for apolipoprotein E4 for Alzheimer’s risk assessment and the anti-BLUE/anti-RAINBOW antibodies for the western blot detection of protein markers.
David Drescher
+43-1-4277-61704
Room: 2.127
Eray Esendir
PostDoc +43-1-4277-61741
Room: 2.130
Ingrid Frohner
PostDoc +43-1-4277-61740
Room: 2.130
Johanna Fromherz
+43-1-4277-61741
Room: 2.130
Sarah Linauer
Technician +43-1-4277-61704
Room: 2.127
Ingrid Mudrak
Lab Manager +43-1-4277-61740
Room: 2.030
Patricia Odermatt
+43-1-4277-61704
Room: 2.127
Egon Ogris
Group Leader +43-1-4277-61730
Room: 2.117
Stefan Schuechner
PostDoc +43-1-4277-61731
Room: 2.127
Alexander Stadler
Technician +43-1-4277-61704
Room: 2.127
Samuel Strobel
Diploma/Master Student +43-1-4277-61730
Room: 2.127
Jiri Veis
PostDoc +43-1-4277-52826
Room: 2.122
Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.
Rasool, Reyaz Ur; O'Connor, Caitlin M; Das, Chandan Kanta; Alhusayan, Mohammed; Verma, Brijesh Kumar; Islam, Sehbanul; Frohner, Ingrid E; Deng, Qu; Mitchell-Velasquez, Erick; Sangodkar, Jaya; Ahmed, Aqila; Linauer, Sarah; Mudrak, Ingrid; Rainey, Jessica; Zawacki, Kaitlin P; Suhan, Tahra K; Callahan, Catherine G; Rebernick, Ryan; Natesan, Ramakrishnan; Siddiqui, Javed; Sauter, Guido; Thomas, Dafydd; Wang, Shaomeng; Taylor, Derek J; Simon, Ronald; Cieslik, Marcin; Chinnaiyan, Arul M; Busino, Luca; Ogris, Egon; Narla, Goutham; Asangani, Irfan A
Selective PP2A Enhancement through Biased Heterotrimer Stabilization.
Leonard, Daniel; Huang, Wei; Izadmehr, Sudeh; O'Connor, Caitlin M; Wiredja, Danica D; Wang, Zhizhi; Zaware, Nilesh; Chen, Yinghua; Schlatzer, Daniela M; Kiselar, Janna; Vasireddi, Nikhil; Schüchner, Stefan; Perl, Abbey L; Galsky, Matthew D; Xu, Wenqing; Brautigan, David L; Ogris, Egon; Taylor, Derek J; Narla, Goutham
PP2AC Phospho-Tyr307 Antibodies Are Not Specific for this Modification but Are Sensitive to Other PP2AC Modifications Including Leu309 Methylation.
Frohner, Ingrid E; Mudrak, Ingrid; Schüchner, Stefan; Anrather, Dorothea; Hartl, Markus; Sontag, Jean-Marie; Sontag, Estelle; Wadzinski, Brian E; Preglej, Teresa; Ellmeier, Wilfried; Ogris, Egon
Antibodies recognizing the C terminus of PP2A catalytic subunit are unsuitable for evaluating PP2A activity and holoenzyme composition.
Frohner, Ingrid E; Mudrak, Ingrid; Kronlachner, Stephanie; Schüchner, Stefan; Ogris, Egon
The Myc tag monoclonal antibody 9E10 displays highly variable epitope recognition dependent on neighboring sequence context.
Schüchner, Stefan; Behm, Christian; Mudrak, Ingrid; Ogris, Egon
The Ogris lab is funded by service and royalty fees from antibody licensing agreements and the monoclonal antibody service facility of the Medical University of Vienna/Max Perutz Labs.
The Group Ogris participates in the special Doctoral Program "Molecular Mechanisms of Cell Signaling" reviewed and funded by the Austrian Research Fund FWF.
Nutrient-regulated control of lysosome function by signaling lipid conversion
14:00 - 15:00
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11:00 - 12:00 GMI Orange Seminar RoomPikobodies: What does it take to bioengineer NLR immune receptor-nanobody fusions
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13:15 - 14:15 UBB - Lecture Hall 1Gene regulatory mechanisms governing human development, evolution and variation
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11:00 - 12:00 IMBA/GMI Lecture HallPhage therapy for treating bacterial infections: a double-edged sword
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11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)SLiMs and SHelMs: Decoding how short linear and helical motifs direct PPP specificity to direct signaling
14:00 - 15:00 MFPL main building, 6th floor SR1/2Title to be announced
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11:00 - 12:00 GMI Orange Seminar RoomBacterial cell envelope homeostasis at the (post)transcriptional level
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14:00 - 15:00 VBC5 Lecture Hall A+B/ZoomHydrologic extremes alter mechanisms and pathways of carbon export from mountainous floodplain soils
12:00 - 13:00 UBB - Lecture Hall 1Dissecting post-transcriptional gene expression regulation in humans and viruses
11:00 - 12:00 IMBA/GMI Lecture HallPolyploidy and rediploidisation in stressful times
13:15 - 14:15 UBB - Lecture Hall 1Prdm9 control of meiotic synapsis of homologs in intersubspecific hybrids
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Title to be announced
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13:15 - 14:15 UBB - Lecture Hall 1Programmed DNA double-strand breaks during meiosis: Mechanism and evolution
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Title to be announced
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