Protein Profiling

The Protein Profiling group provides comprehensive, cutting-edge discovery proteomic and integrated bioinformatics expertise for the Unit Programmes.

The group specialises in using shotgun proteomics and label-free quantitative analysis of proteins and protein complexes. We use a variety of techniques, including affinity purification, gel filtration chromatography, sub-cellular fractionation and organelle purification to maximise protein identification and quantitative analysis.  The group collaboratively interacts with Unit research staff to plan, execute and publish innovative research papers. The group has two ‘state of the art’ Waters Synapt G2 mass spectrometers equipped with nanoAcquity UPLC chromatography systems. Advanced bioinformatics analysis on Mass spectrometry data is carried our using Proteomics Linked Global, Scaffold Proteome and Progenesis Transomics software.

Key areas in which the group are currently involved include:

1) Mitochondrial proteomic analysis and effects of metabolic regulation.

2) Death receptor complexes.

3) Analysis of DNA repair complexes.

4) RNA binding proteins.

5) Identification of proteins involved in protein translation/initiation.

Selected Publications

Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate.

Hughes MA, Powley IR, Jukes-Jones R, Horn S, Feoktistova M, Fairall L, Schwabe JW, Leverkus M, Cain K, MacFarlane M.

Mol Cell. 2016 Mar 17;61(6):834-49. doi: 10.1016/j.molcel.2016.02.023.

XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair.

Craxton A, Somers J, Munnur D, Jukes-Jones R, Cain K, Malewicz M.

Cell Death Differ. 2015 Jun;22(6):890-7. doi: 10.1038/cdd.2015.22.

Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs.

King HA, Cobbold LC, Pichon X, Pöyry T, Wilson LA, Booden H, Jukes-Jones R, Cain K, Lilley KS, Bushell M, Willis AE.

Cell Death Differ. 2014 Jan;21(1):161-71. doi: 10.1038/cdd.2013.135.

A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death.

Dickens LS, Boyd RS, Jukes-Jones R, Hughes MA, Robinson GL, Fairall L, Schwabe JW, Cain K, Macfarlane M.

Mol Cell. 2012 Jul 27;47(2):291-305. doi: 10.1016/j.molcel.2012.05.004.

Glucose–a sweet way to die: metabolic switching modulates tumor cell death.

MacFarlane M, Robinson GL, Cain K.

Cell Cycle. 2012 Nov 1;11(21):3919-25. doi: 10.4161/cc.21804.

cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms.

Feoktistova M, Geserick P, Kellert B, Dimitrova DP, Langlais C, Hupe M, Cain K, MacFarlane M, Häcker G, Leverkus M.

Mol Cell. 2011 Aug 5;43(3):449-63. doi: 10.1016/j.molcel.2011.06.011.

The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs.

Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, Wallberg F, Zachariou A, Lopez J, MacFarlane M, Cain K, Meier P.

Mol Cell. 2011 Aug 5;43(3):432-48. doi: 10.1016/j.molcel.2011.06.006.

Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration.

Bartesaghi S, Betts-Henderson J, Cain K, Dinsdale D, Zhou X, Karlsson A, Salomoni P, Nicotera P.

Hum Mol Genet. 2010 May 1;19(9):1669-77. doi: 10.1093/hmg/ddq043.

HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.

Capasso M, Bhamrah MK, Henley T, Boyd RS, Langlais C, Cain K, Dinsdale D, Pulford K, Khan M, Musset B, Cherny VV, Morgan D, Gascoyne RD, Vigorito E, DeCoursey TE, MacLennan IC, Dyer MJ.

Nat Immunol. 2010 Mar;11(3):265-72. doi: 10.1038/ni.1843.

Protein profiling of plasma membranes defines aberrant signaling pathways in mantle cell lymphoma.

Boyd RS, Jukes-Jones R, Walewska R, Brown D, Dyer MJ, Cain K.

Mol Cell Proteomics. 2009 Jul;8(7):1501-15. doi: 10.1074/mcp.M800515-MCP200.

Reconstitution of the death-inducing signaling complex reveals a substrate switch that determines CD95-mediated death or survival.

Hughes MA, Harper N, Butterworth M, Cain K, Cohen GM, MacFarlane M.

Mol Cell. 2009 Aug 14;35(3):265-79. doi: 10.1016/j.molcel.2009.06.012.

Caspase-7 is directly activated by the approximately 700-kDa apoptosome complex and is released as a stable XIAP-caspase-7 approximately 200-kDa complex.

Twiddy D, Cohen GM, Macfarlane M, Cain K.

J Biol Chem. 2006 Feb 17;281(7):3876-88.

Pro-apoptotic proteins released from the mitochondria regulate the protein composition and caspase-processing activity of the native Apaf-1/caspase-9 apoptosome complex.

Twiddy D, Brown DG, Adrain C, Jukes R, Martin SJ, Cohen GM, MacFarlane M, Cain K.

J Biol Chem. 2004 May 7;279(19):19665-82.

The Apaf-1 apoptosome: a large caspase-activating complex.

Cain K, Bratton SB, Cohen GM.

Biochimie. 2002 Feb-Mar;84(2-3):203-14.

Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex.

Cain K, Brown DG, Langlais C, Cohen GM.

J Biol Chem. 1999 Aug 6;274(32):22686-92.

Protein Profiling Group

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