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Pseudoenzymes 2016: from Signalling Mechanisms to Disease

11—14 September 2016

Liverpool Maritime Museum, UK

Pseudoenzymes can be defined as ‘proteins that are unable to catalyse chemical reactions compared to enzyme paralogues’, and until recently, their inclusion in a scientific agenda might have raised eyebrows. 

However, the realisation that 5-10% of gene families encoding proteases, kinases and phosphatases are in fact pseudoenzymes, which have recently become recognised as essential regulators of biological processes, has led to much interest amongst bioinformaticians, structural biochemists, cell biologists, chemists and clinicians. 

As our knowledge of pseudoenzyme function advances, it has emerged that detailed study of these proteins have also yielded unexpected fundamental insights into non-catalytic functions of their active counterparts. An interesting twist on the emergence of important signalling roles for pseudoenzymes is that since enzymes are major small molecule targets, pseudoenzymes probably also make up a major class of disease targets that we are knowingly (or more likely unknowingly) already modulating with drugs. 

To celebrate, nurture and advance this exciting field, the world’s first dedicated pseudoenzyme meeting will take place in Liverpool in September 2016. This meeting brings together current experts in the field to help shape thinking and to capitalise on our knowledge of genomes and proteomes to advance the pseudoenzyme field into the 21st century.

Major themes that will be explored at this meeting include:

·         Evolution of pseudoenzymes

·         Biochemistry and cell biology of pseudoenzymes

·         Systems Biology of pseudoenzymes

·         Pseudoenzymes in disease

·         Pseudoenzymes as therapeutic targets

·         Emerging areas in pseudoenzmye biology

Patrick Eyers (University of Liverpool, United Kingdom)
Hesso Farhan (University of Oslo, Norway)
James Murphy (Walter and Eliza Hall Institute of Medical Research, Australia)
Sunday 11 September 2016
12:00 - 14:00 Registration and Lunch

14:00 - 14:10 Introduction and Welcome

14:10 - 14:55
How CDKs control the cell cycle
Keynote Speaker - Sir Paul Nurse (The Francis Crick Institute, United Kingdom)
15:00 - 15:15
Careers and Gender
Janet Beer (University of Liverpool, United Kingdom)
15:20 - 16:00 Tea/Coffee Break

16:05 - 16:35
Unraveling pseudoenzyme regulatory mechanisms using an evolutionary-systems approach
Natarajan Kannan (University of Georgia, U.S.A.)
16:40 - 16:55
Pseudokinases in UniProtKB: a curator point-of-view
Selected Oral Communication- Rossanna Zaru (EMBL, United Kingdom)
17:00 - 17:45
Keynote Speaker- Gerard Manning (Genentech, U.S.A.)
17:45 Drinks Reception

Monday 12 September 2016
08:50 - 09:00 Welcome and Announcements

09:00 - 09:45
The Evolution of Enzyme Function
Keynote Speaker - Janet Thornton (European Bioinformatics Inst., United Kingdom)
09:50 - 10:00
Pseudokinase occurrences in families of the protein kinase-like clan. Biological relevance?
Selected Oral Communication- Krzysztof Pawlowski (University of Warsaw, Poland)
10:10 - 10:40
Towards discovery: from pseudoenzymes to pseudosignalers?
Hans Westerhoff (University of Amsterdam, Netherlands)
10:45 - 11:00
Metal coordination as a distinguishing Feature between Kinase and Pseudokinase Function
Selected Oral Communication- Friedrich Herberg (University of Kassel, Germany)
11:05 - 11:45 Tea/ Coffee Break

11:45 - 12:15
The roles of RIPK1, RIPK3, and MLKL in cell death
Kim Newton (Genentech, U.S.A.)
12:20 - 12:35
Death's own chaperone: unravelling the relationship between HSP90 and the killer pseudokinase MLKL
Selected Oral Communication- Annette Jacobsen (The Walter and Eliza Hall Institute of Medical Research, Australia)
12:40 - 12:55
The secret life of kinases: insights into non-catalytic functions from our studies of the pseudokinase, MLKL
James Murphy (Walter and Eliza Hall Institute of Medical Research, Australia)
13:00 - 14:00 Lunch

13:40 - 14:00 Careers Session- Presentations and Q&A

14:00 - 14:30
Characterization of P-REX1 function in human breast cancer.
Christina Mitchell (Monash University, Australia)
14:35 - 14:50
Aurora-A acts as a molecular scaffold to stabilize N-Myc
Selected Oral Communication- Richard Bayliss (University of Leeds, United Kingdom)
14:55 - 15:25
The FAM83 family of proteins: Pseudo-PLDs?
Gopal Sapkota (University of Dundee, United Kingdom)
15:30 - 16:00 Tea/Coffee Break

16:00 - 16:30
Allosteric Activation of Deubiquitinating Enzymes (DUBs) by Inactive Pseudo-DUBs
Elton Zeqiraj (Lunenfeld-Tanenbaum Research Institute, Toronto, Canada)
16:35 - 17:00
Allosteric regulation of the anchored protein kinase A holoenzyme: are the catalytic subunits released in situ?
Selected Oral Communication- John Scott (University of Washington, USA)
17:00 - 17:45
Lessons learned from PKA: From motifs to allosteric molecular switches
Keynote Speaker - Susan Taylor (University of California San Diego, U.S.A.)
17:50 - 19:30 Drinks Reception/ Poster Session

Tuesday 13 September 2016
09:00 - 09:45
Rhomboid-like proteases and pseudoproteases
Keynote Speaker - Matthew Freeman (Sir William Dunn School of Pathology, University of Oxford, United Kingdom)
09:50 - 10:00
Functional studies of trypanosomatid deoxyhypusine synthase as drug target
Selected Oral Communication- Gustavo Afanador (UT Southwestern Medical Center, USA)
10:10 - 10:40
A bacterial pseudokinase regulates asymmetric cell division in a bacterium
Seth Childers (University of Pittsburgh, U.S.A.)
10:45 - 11:00
Phosphorylation of spore coat proteins by a family of atypical protein kinases
Selected Oral Communication-Vincent Tagliabracci (UT Southwestern Medical Center, USA)
11:00 - 11:30 Tea/ Coffee Break

11:35 - 11:50
Novel, apparently rare mitochondrial histidine phosphatases in kinetoplastid protists: the interaction of catalytic and catalytically-‘dead’ paralogues and the enigma of their function
Selected Oral Communication- Michael Ginger (University of Huddersfield, United Kingdom)
11:55 - 12:25
New insights into control of HER3 receptor pseudokinase signaling
Natalia Jura (University of California San Francisco, U.S.A.)
12:30 - 13:00
Arnim Pause (McGill University)
13:00 - 14:00 Lunch

14:00 - 16:00 Free time

16:00 - 16:30
Pseudophosphatase MK-STYX Regulates Neurite Outgrowth
Shantá Hinton (College of Wiliam and Mary, U.S.A.)
16:35 - 17:05
The pseudophosphatase STYX regualtes the FBXW7 tumor suppressor
Hesso Farhan (University of Oslo, Norway)
17:10 - 17:40
What constitutes a pseudophosphatase? – A cautionary tale of PTPN23 as a tumor suppressor in breast tumorigenesis
Nicholas Tonks (Cold Spring Harbor Laboratory, U.S.A.)
17:30 - 19:30 Drinks reception, Beer Tasting & Poster Session

20:00 Conference Dinner

Wednesday 14 September 2016
09:00 - 09:30
Pharmacological profiling identifies ROR1-targeted treatment strategies for hematological malignancies
Daniela Ungureanu (University of Tempere, Finland)
09:35 - 09:50
The absence of TRIB2 pseudokinase positively regulates AML cell cycle progression and survival of DNA damaged cells
Selected Oral Communication- Mara Salome (University of Glasgow, United Kingdom)
09:55 - 10:25
Substrate-based regulation of the TRIB1 pseudokinase
Peter Mace (University of Otago, New Zealand)
10:30 - 10:45
UNC-89 pseudokinases: disparate active sites with unusual properties
Selected Oral Communication- Thomas Zacharchenko (University of Leeds, United Kingdom)
10:45 - 11:15 Tea/ Coffee Break

11:15 - 11:30
A Phosphorylation-dependent Negative Charge Patch In the Pseudo-kinase Domain Is Required for Activation of Guanylyl Cyclase-A
Selected Oral Communication- Lincoln Potter (University of Minnesota, USA)
11:35 - 12:05
The molecular Jekyll and Hyde role of TRIB2 in leukaemia
Karen Keeshan (University of Glasgow, United Kingdom)
12:10 - 12:25
Patrick Eyers (University of Liverpool, United Kindom)
12:30 - 12:45 Closing Remarks

12:45 Lunch and Depart