Understanding How Cytotoxic Lymphocytes Protect Against Cancer

Defining the interaction of perforin with calcium and the phospholipid membrane

DAK Traore, AJ Brennan, RHP Law, C Dogovski, MA Perugini, N Lukoyanova, EWW Leung, RS Norton, JA Lopez, KA Browne, H Yagita, GJ Lloyd, A Ciccone, S Verschoor, JA Trapani, JC Whisstock, I Voskoboinik

2013-12-15

Following its secretion from cytotoxic lymphocytes into the immune synapse, perforin binds to target cell membranes through its Ca..

Exploration of a series of 5-arylidene-2-thioxoimidazolidin-4-ones as inhibitors of the cytolytic protein perforin

JA Spicer, G Lena, DM Lyons, KM Huttunen, CK Miller, PD O'Connor, M Bull, N Helsby, SMF Jamieson, WA Denny, A Ciccone, KA Browne, JA Lopez, J Rudd-Schmidt, I Voskoboinik, JA Trapani

2013-12-12

A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming..

Perforinopathy: A spectrum of human immune disease caused by defective perforin delivery or function

I Voskoboinik, JA Trapani

2013-12-01

Congenital perforin deficiency is considered a rare cause of human immunopathology and immune dysregulation, and classically prese..

Mouse granzyme A induces a novel death with writhing morphology that is mechanistically distinct from granzyme B-induced apoptosis

O Susanto, SE Stewart, I Voskoboinik, D Brasacchio, M Hagn, S Ellis, S Asquith, KA Sedelies, PI Bird, NJ Waterhouse, JA Trapani

2013-09-01

Human and mouse granzyme (Gzm)B both induce target cell apoptosis in concert with pore-forming perforin (Pfp); however the mechani..

Rapid and unidirectional perforin pore delivery at the cytotoxic immune synapse

JA Lopez, MR Jenkins, JA Rudd-Schmidt, AJ Brennan, JC Danne, SI Mannering, JA Trapani, I Voskoboinik

2013-09-01

The effective engagement of cytotoxic lymphocytes (CLs) with their target cells is essential for the removal of virus-infected and..

Human perforin mutations and susceptibility to multiple primary cancers

JA Trapani, KYT Thia, M Andrews, ID Davis, C Gedye, P Parente, S Svobodova, J Chia, K Browne, IG Campbell, WA Phillips, I Voskoboinik, JS Cebon

2013-04-01

Loss-of-function mutations in the gene coding for perforin (PRF1) markedly reduce the ability of cytotoxic T lymphocytes and natur..

Surprisingly variable ''dangers, toils, and snares'' faced by humans and mice

JA Trapani, I Voskoboinik

2013-01-24

Perforin forms transient pores on the target cell plasma membrane to facilitate rapid access of granzymes during killer cell attack

JA Lopez, O Susanto, MR Jenkins, N Lukoyanova, VR Sutton, RHP Law, A Johnston, CH Bird, PI Bird, JC Whisstock, JA Trapani, HR Saibil, I Voskoboinik

2013-01-01

Cytotoxic lymphocytes serve a key role in immune homeostasis by eliminating virus-infected and transformed target cells through th..

Protecting a serial killer: Pathways for perforin trafficking and self-defence ensure sequential target cell death

JA Lopez, AJ Brennan, JC Whisstock, I Voskoboinik, JA Trapani

2012-08-01

Considerable progress has been made in understanding how cytotoxic lymphocytes use the highly toxic pore-forming protein perforin ..

Fatal immune dysregulation due to a gain of glycosylation mutation in lymphocyte perforin

J Chia, K Thia, AJ Brennan, M Little, B Williams, JA Lopez, JA Trapani, I Voskoboinik

2012-02-16

Mutations in the perforin gene (PRF1) are a common cause of the fatal immune dysregulation disorder, familial hemophagocytic lymph..

Protection from Endogenous Perforin: Glycans and the C Terminus Regulate Exocytic Trafficking in Cytotoxic Lymphocytes

AJ Brennan, J Chia, KA Browne, A Ciccone, S Ellis, JA Lopez, O Susanto, S Verschoor, H Yagita, JC Whisstock, JA Trapani, I Voskoboinik

2011-06-24

Cytotoxic lymphocyte-mediated apoptosis is dependent on the delivery of perforin to secretory granules and its ability to form cal..

Cytotoxic granules house potent proapoptotic toxins critical for antiviral responses and immune homeostasis

K Baran, I Voskoboinik, NJ Waterhouse, VR Sutton, JA Trapani

2011-01-01

General Introduction Cytotoxic lymphocytes and apoptosis The immune system of high-order organisms is a highly specialized compart..

The structural basis for membrane binding and pore formation by lymphocyte perforin

RHP Law, N Lukoyanova, I Voskoboinik, TT Caradoc-Davies, K Baran, MA Dunstone, ME D'Angelo, EV Orlova, F Coulibaly, S Verschoor, KA Browne, A Ciccone, MJ Kuiper, PI Bird, JA Trapani, HR Saibil, JC Whisstock

2010-11-18

Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neopla..

The structure and function of mammalian membrane-attack complex/perforin-like proteins

SC Kondos, T Hatfaludi, I Voskoboinik, JA Trapani, RHP Law, JC Whisstock, MA Dunstone

2010-11-01

The membrane-attack complex (MAC) of complement pathway and perforin (PF) are important tools deployed by the immune system to tar..

Perforin: Structure, function, and role in human immunopathology

I Voskoboinik, MA Dunstone, K Baran, JC Whisstock, JA Trapani

2010-05-01

The secretory granule-mediated cell death pathway is the key mechanism for elimination of virus-infected and transformed target ce..

Perforin deficiency and susceptibility to cancer

AJ Brennan, J Chia, JA Trapani, I Voskoboinik

2010-04-01

Cytotoxic lymphocytes (CLs) are the killer cells that destroy intracellular pathogen-infected and transformed cells, predominantly..

The battlefield of perforin/granzyme cell death pathways

S Hoves, JA Trapani, I Voskoboinik

2010-02-01

A pore-forming protein, PRF, and serine proteases, Grz, are key effector molecules of CL. These toxins are stored within secretory..