Professor Neil Perkins
Prof of Gene Exp & Signalling
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 208 8866
- Fax: +44 (0) 191 208 7424
- Address: Institute for Cell and Molecular Biosciences (ICaMB)
Catherine Cookson Building
Newcastle upon Tyne
My PhD was completed in Graham Goodwin's laboratory at the Chester Beatty Laboratories, Institute of Cancer Research, London in 1990. This work concerned the investigation of chicken beta globin gene expression and resulted in the identification of the transcription factor that later became known as GATA1 (known as EF1 in the Goodwin lab).
From 1990 to 1996 I was a postdoctoral researcher in Gary Nabel's laboratory, at the Howard Hughes Medical Institute at the University of Michigan, where my interest in the NF-κB transcription factor family began. Much of this work concerned the ability of NF-κB to function as a regulator of human immunodeficiency virus (HIV) 1.
October 1986 - March 1990: Ph.D. student in the laboratory of Dr. Graham Goodwin, Chester Beatty Laboratories, Institute of Cancer Research.
March 1990- March 1996: Postdoctoral Fellow in the laboratory of Prof. Gary J. Nabel, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI, USA.
March 1996 – Nov 2007: Lecturer and then Reader, Principal Investigator, University of Dundee
October 1996 - September 2005: Royal Society University Research Fellow
Nov 2007 – June 2008: Professor of Gene Expression and Signalling in the Wellcome Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee
July 2008 – March 2010: Professor of Molecular Cell Biology, Department of Cellular & Molecular Medicine, University of Bristol
April 2010 - present: Professor of Gene Expression and Signalling, Newcastle University
Regulation of cancer cell proliferation and survival by NF-κB
NF-κB is a collective name for the complexes formed by the multigene NF-κB-Rel family which function as DNA-binding proteins and transcription factors. NF-κB subunits induce the expression of a wide range of genes encoding proteins involved in inflammation, regulation of cell death, cell adhesion, proliferation and other critical cellular functions. Aberrant activation of NF-κB therefore leads to overproduction of these proteins, which can contribute to many types of human disease. In particular, NF-κB has an important role in many inflammatory diseases and cancer. Moreover, NF- κB is activated by many cancer therapies and can have an inhibitory effect on these treatments. The pathways regulating NF-κB are therefore thought to be good targets for the development of new anti-inflammatory and anti-cancer drugs.
My laboratory is interested in how NF-κB subunits are regulated by oncogenes, tumour suppressors and stimuli associated with cancer development and therapy. A theme emerging from these studies has been the importance of context for NF-κB activity and how subunits can both repress as well as activate gene targets, leading to alterations in cell fate. We have revealed the importance of post-translational modifications in controlling these activities and argued that the activity of parallel signaling pathways have a critical role in determining NF-κB dependent transcriptional output. Based on this work, together with that from other researchers, we propose that the concerted action of tumour suppressors functions to keep the oncogenic activities of NF-κB subunits in check and that loss of tumour suppressor activity during tumour development is required to unleash these anti apoptotic and pro-metastatic activities in malignant cancer cells.
We are also interested in a protein known as Smad nuclear interacting protein 1 (SNIP1). We have previously described SNIP1 as a regulator of Cyclin D1 expression. Recently we have identified a SNIP1 containing complex and demonstrated that this functions as a novel regulator of Cyclin D1 RNA stability.
- Willmore E, Gardner A, Tudhope S, Murtani B, Caffry J, Mulligan E, Hunter J, Wallis J, Marr H, Beretta G, Breen D, Paul A, Edwards D, Young L, Suckling C, Plevin R, Boyd M, Mackay S, Perkins N. Novel small molecule IKK alpha inhibitors inhibit non- canonical NF-kappa B signaling and survival of primary CLL cells. In: XVI International Workshop on Chronic Lymphocytic Leukemia. 2015, Sydney, Australia: Taylor & Francis.
- Yamada K, Ono M, Perkins ND, Rocha S, Lamond AI. Identification and Functional Characterization of FMN2, a Regulator of the Cyclin-Dependent Kinase Inhibitor p21. Molecular Cell 2013, 49(5), 922-933.
- Moles A, Sanchez AM, Banks PS, Murphy LB, Luli S, Borthwick L, Fisher A, O'Reilly S, van Laar JM, White SA, Perkins ND, Burt AD, Mann DA, Oakley F. Inhibition of RelA-Ser536 phosphorylation by a competing peptide reduces mouse liver fibrosis without blocking the innate immune response. Hepatology 2013, 57(2), 817-828.
- Southern SL, Collard TJ, Urban BC, Skeen VR, Smartt HJ, Hague A, Oakley F, Townsend PA, Perkins ND, Paraskeva C, Williams AC. BAG-1 interacts with the p50-p50 homodimeric NF-kappa B complex: implications for colorectal carcinogenesis. Oncogene 2012, 31(22), 2761-2772.
- Perkins ND. Cysteine 38 Holds the Key to NF-kappa B Activation. Molecular Cell 2012, 45(1), 1-3.
- Johnson RF, Perkins ND. Nuclear factor-kappa B, p53, and mitochondria: regulation of cellular metabolism and the Warburg effect. Trends in Biochemical Sciences 2012, 37(8), 317-324.
- Perkins ND. The diverse and complex roles of NF-kappa B subunits in cancer. Nature Reviews. Cancer 2012, 12(2), 121-132.
- Johnson RF, Witzel II, Perkins ND. p53-dependent regulation of mitochondrial energy production by the RelA subunit of NF-κB. Cancer Research 2011, 71(16), 5588-5597.
- Msaki A, Sanchez AM, Koh LF, Barre B, Rocha S, Perkins ND, Johnson RF. The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration. Molecular Biology of the Cell 2011, 22(17), 3032-3040.
- McKenzie L, King S, Marcar L, Nicol S, Dias SS, Schumm K, Robertson P, Bourdon JC, Perkins N, Fuller-Pace F, Meek DW. p53-dependent repression of polo-like kinase-1 (PLK1). Cell Cycle 2010, 9(20), 4200-4212.
- Witzel II, Koh LF, Perkins ND. Regulation of cyclin D1 gene expression. In: Biochemical Society Transactions: 13th Tenovus Scotland Symposium - Gene Expression in Development and Disease. 2010, Glasgow, UK: Portland Press Ltd.
- O'Shea JM, Perkins ND. Thr(435) phosphorylation regulates RelA (p65) NF-kappa B subunit transactivation. Biochemical Journal 2010, 426(3), 345-354.
- Perkins ND. [abstract] Regulation of cancer cell proliferation and survival by NF-kappa B. International Journal of Molecular Medicine 2009, 24(s1), S22 abstract no. 169.
- Gilmore TD, Perkins ND, Franzoso G. Getting away from it all in Capri: the 2008 EMBO workshop on NF-kappa B. Cell Death & Differentiation 2009, 16(4), 651-654.
- Granja AG, Perkins ND, Revilla Y. A238L inhibits NF-ATc2, NF-kappa B, and c-Jun activation through a novel mechanism involving protein kinase C-theta-mediated up-regulation of the amino-terminal transactivation domain of p300. Journal of Immunology 2008, 180(4), 2429-2442.
- Arlt A, Rosenstiel P, Kruse ML, Grohmann F, Minkenberg J, Perkins ND, Folsch UR, Schreiber S, Schafer H. IEX-1 directly interferes with RelA/p65 dependent transactivation and regulation of apoptosis. Biochimica et Biophysica Acta: Molecular Cell Research 2008, 1783(5), 941-952.
- Bracken CP, Wall SJ, Barré B, Panov KI, Ajuh PM, Perkins ND. Regulation of cyclin D1 RNA stability by SNIP1. Cancer Research 2008, 68(18), 7621-7628.
- O'Shea JM, Perkins ND. Regulation of the ReIA (p65) transactivation domain. Biochemical Society Transactions 2008, 36(4), 603-608.
- Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nature Reviews Molecular Cell Biology 2007, 8(1), 49-62.
- Tergaonkar V, Perkins ND. p53 and NF-κB crosstalk: IKKα tips the balance. Molecular Cell 2007, 26(2), 158-159.
- McTavish N, Copeland LA, Saville MK, Perkins ND, Spruce BA. Proenkephalin assists stress-activated apoptosis through transcriptional repression of NF-kappaB- and p53-regulated gene targets. Cell Death and Differentiation 2007, 14(9), 1700-1710.
- Roche KC, Rocha S, Bracken CP, Perkins ND. Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1. Oncogene 2007, 26(31), 4523-4530.
- Sharif O, Bolshakov VN, Raines S, Newham P, Perkins ND. Transcriptional profiling of the LPS induced NF-κB response in macrophages. BMC Immunology 2007, 8, 1.
- Campbell KJ, Witty JM, Rocha S, Perkins ND. Cisplatin mimics ARF tumor suppressor regulation of RelA (p65) nuclear factor-kappaB transactivation. Cancer Research 2006, 66(2), 929-935.
- Campbell KJ, O'Shea JM, Perkins ND. Differential regulation of NF-κB activation and function by topoisomerase II inhibitors. BMC Cancer 2006, 6, 101.
- Perkins ND, Gilmore TD. Good cop, bad cop: the different faces of NF-kappaB. Cell Death and Differentiation 2006, 13(5), 759-772.
- Perkins ND. Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene 2006, 25(51), 6717-6730.
- Schumm K, Rocha S, Caamano J, Perkins ND. Regulation of p53 tumour suppressor target gene expression by the p52 NF-kappaB subunit. The EMBO Journal 2006, 25(20), 4820-4832.
- Fujii M, Lyakh LA, Bracken CP, Fukuoka J, Hayakawa M, Tsukiyama T, Soil SJ, Harris M, Rocha S, Roche KC, Tominaga SI, Jen J, Perkins ND, Lechleider RJ, Roberts AB. SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes. Molecular Cell 2006, 24(5), 771-783.
- Rocha S, Perkins ND. ARF the integrator: linking NF-kappaB, p53 and checkpoint kinases. Cell Cycle 2005, 4(6), 756-759.
- Fu MF, Wang CG, Rao M, Wu XF, Bouras T, Zhang XP, Li ZP, Jiao XM, Yang JG, Li AP, Perkins ND, Thimmapaya B, Kung AL, Munoz A, Giordano A, Lisanti MP, Pestell RG. Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. Journal of Biological Chemistry 2005, 280(33), 1113-1119.
- Cheng JK, Perkins ND, Yeh ETH. Differential regulation of c-Jun-dependent transcription by SUMO-specific proteases. Journal of Biological Chemistry 2005, 280(15), 14492-14498.
- Garcia-Wilson E, Perkins ND. p21(WAF1/CIP1) regulates the p300 sumoylation motif CRD1 through a C-terminal domain independently of Cyclin/CDK binding. Cell Cycle 2005, 4(8), 1113-1119.
- Rocha S, Garrett MD, Campbell KJ, Schumm K, Perkins ND. Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. The EMBO Journal 2005, 24(6), 1157-1169.
- Campbell KJ, Perkins ND. Regulation of NF-kappaB function. In: 73rd Biochemical Society Symposium. 2005, Imperial College, London: Biochemical Society.
- Bouras T, Fu MF, Sauve AA, Wang F, Quong AA, Perkins ND, Hay RT, Gu W, Pestell RG. SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. Journal of Biological Chemistry 2005, 280(11), 10264-10276.
- Bates GJ, Nicol SM, Wilson BJ, Jacobs AMF, Bourdon JC, Wardrop J, Gregory DJ, Lane DP, Perkins ND, Fuller-Pace FV. The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. The EMBO Journal 2005, 24(3), 543-553.
- Moles A, Butterworth JA, Sanchez A, Hunter JE, Leslie J, Sellier H, Tiniakos D, Cockell SJ, Mann DA, Oakley F, Perkins ND. A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-kB dependent liver regeneration and cancer. Oncogene 2016, 35(35), 4623–4632.
- Hunter JE, Leslie J, Perkins ND. c-Rel and its many roles in cancer: an old story with new twists. British Journal of Cancer 2016, 114(1), 1-6.
- Cartwright T, Perkins ND, Wilson CL. NFKB1: a suppressor of inflammation, ageing and cancer. FEBS Journal 2016, 283(10), 1812-1822.
- Walton MI, Eve PD, Hayes A, Henley AT, Valenti MR, Brandon AKD, Box G, Boxall KJ, Tall M, Swales K, Matthews TP, McHardy T, Lainchbury M, Osborne J, Hunter JE, Perkins ND, Aherne GW, Reader JC, Raynaud FI, Eccles SA, Collins I, Garrett MD. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eμ-MYC driven B-cell lymphoma. Oncotarget 2016, 7(3), 2329-2342.
- Perkins ND. The importance of the p50 NF-κB subunit. Cell Cycle 2015, 14(18), 2877-2878.
- Hunter JE, Butterworth JA, Zhao B, Sellier H, Campbell KJ, Thomas HD, Bacon CM, Cockell SJ, Gewurz BE, Perkins ND. The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma. Oncogene 2015, epub ahead of print.
- Moles A, Butterworth J, Hunter JE, Sanchez AM, Tiniakos D, Mann D, Oakley F, Perkins ND. Thr505 RelA phosphorylation controls liver proliferative response and supresses NF-kappa B tumor-promoting activities. In: 66th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2015. 2015, San Francisco, California: John Wiley & Sons, Inc.
- Tavora B, Reynolds LE, Batista S, Demircioglu F, Fernandez I, Lechertier T, Lees DM, Wong PP, Alexopoulou A, Elia G, Clear A, Ledoux A, Hunter J, Perkins N, Gribben JG, Hodivala-Dilke KM. Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy. Nature 2014, 514(7520), 112-116.
- Bonacci T, Audebert S, Camoin L, Baudelet E, Bidaut G, Garcia M, Witzel II, Perkins ND, Borg JP, Iovanna JL, Soubeyran P. Identification of New Mechanisms of Cellular Response to Chemotherapy by Tracking Changes in Post-Translational Modifications by Ubiquitin and Ubiquitin-Like Proteins. Journal of Proteome Research 2014, 13(5), 2478-2494.
- Ledoux AC, Perkins ND. NF-kB and the cell cycle. Biochemical Society Transactions 2014, 42(1), 76-81.
- Harte MT, Gorski JJ, Savage KI, Purcell JW, Barros EW, Burn PM, McFarlane C, Mullan PB, Kennedy RD, Perkins ND, Harkin DP. NF-kappa B is a critical mediator of BRCA1-induced chemoresistance. Oncogene 2014, 33(6), 713-723.
- Iannetti A, Ledoux AC, Tudhope SJ, Sellier H, Zhao B, Mowla S, Moore A, Hummerich H, Gewurz BE, Cockell SJ, Jat PS, Willmore E, Perkins ND. Regulation of p53 and Rb Links the Alternative NF-kappa B Pathway to EZH2 Expression and Cell Senescence. PLoS Genetics 2014, 10(9).
- Hunter JE, Butterworth J, Perkins ND, Bateson M, Richardson CA. Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eμ-myc lymphoma. British Journal of Cancer 2014, 110, 928-934.
- Perkins ND. Emerging from NF-kappa B's Shadow, SUMOylated I kappa B alpha Represses Transcription. Cancer Cell 2013, 24(2), 139-140.
- Ledoux AC, Sellier H, Gillies K, Iannetti A, James J, Perkins ND. NF kappa B regulates expression of Polo-like kinase 4. Cell Cycle 2013, 12(18), 3052-3062.