Academic Staff
Professor Neil Perkins
Professor of Molecular Cell Biology
Contact Details
Dept. of Cellular & Molecular Medicine, University of Bristol,
School of Medical Sciences, Bristol, BS8 1TD
Tel: +44 (0)117 33 12045 (internal: 12045)
Fax: +44 (0)117 33 12091
Email: N.D.Perkins@bristol.ac.uk
Neil Perkins has recently moved to Bristol from the College of Life Sciences, University of Dundee
Past Research
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.
Current Research
Nuclear Factor kappaB (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. Typically, in non-stimulated normal cells, NF-κB subunits are held in an inactive cytoplasmic form. In response to cellular stimulation, typical examples of which are exposure to the inflammatory cytokines tumour necrosis factor α (TNFα) and interleukin 1 (IL-1), NF-κB translocates to the nucleus where it can regulate gene expression.
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 over-production 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. In particular, we have found that the ARF and p53 tumour suppressors as well as certain inducers of NF-κB DNA-binding activity, such as ultraviolet light and some chemotherapeutic compounds, can induce the association of NF-κB subunits with transcriptional corepressor complexes, allowing them to function as repressors rather than activators of gene expression. The identification of these pathways suggests that NF-κB can function as a tumour suppressor as well as a tumour promoter. We are investigating the mechanisms regulating these pathways and also the implications of these results for both traditional and NF-κB based cancer therapy.
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.
Present co-workers
- Benjamin Barré
- Tom Curry
- Renee Johnson
- Lifang Koh
- Adeline Ledoux
- John O'Shea
- Ana Sanchez
- Ini Witzel
Recent Publications
Bracken, C.P., Wall, S.J., Barré, B., Panov, K.I., Ajuh, P.M. and Perkins, N.D. (2008) Regulation of Cyclin D1 RNA stability by SNIP1. Cancer Res. Sep 15; 68(18).
Barré, B. and Perkins, N.D. (2007) A cell cycle regulatory network controlling NF-kappaB subunit activity and function. EMBO J. Nov 28; 26(23), 4841-4855.
Tergaonkar, V. and Perkins, N.D. (2007) p53 and NF-kappaB crosstalk: IKKalpha tips the balance. Mol. Cell. Apr 27; 26(2), 158-159. Review
Roche, K.C., Rocha, S., Bracken, C.P. and Perkins, N.D. (2007) Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1. Oncogene Jul 5; 26(31), 4523-4530.
Perkins, N.D. (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat. Rev Mol. Cell Biol. 8(1), 49-62. Review.
Fujii, M., Lyakh, L.A., Bracken, C.P., Fukuoka, J., Hayakawa, M., Tsukiyama, T., Soll, S.J., Harris, M., Rocha, S., Roche, K.C., Tominaga, S., Jen, J., Perkins, N.D., Lechleider, R.J. and Roberts, A.B. (2006) SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes. Mol. Cell. Dec 8; 24(5), 771-783.
Perkins, N.D. (2006) Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene Oct 30; 25(51), 6717-6730. Review.
Schumm, K., Rocha, S., Caamano, J. and Perkins, N.D. (2006) Regulation of p53 tumour suppressor target gene expression by the p52 NF-kappaB subunit. EMBO J. Oct 18; 25(20), 4820-4832.
Campbell, K.J., Witty, J.M., Rocha, S. and Perkins, N.D. (2006) Cisplatin mimics ARF tumor suppressor regulation of RelA (p65) nuclear factor-kappaB transactivation. Cancer Res. Jan 15; 66(2), 929-935.
Perkins, N.D. and Gilmore, T.D. (2006) Good cop, bad cop: the different faces of NF-kappaB. Cell Death Differ. May; 13(5), 759-772. Review
Rocha, S., Garrett, M.D., Campbell, K.J., Schumm, K. and Perkins, N.D. (2005) Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. EMBO J. Mar 23; 24(6), 1157-1169.
Bates, G.J., Nicol, S.M., Wilson, B.J., Jacobs, A.M., Bourdon, J.C., Wardrop, J., Gregory, D.J., Lane, D.P., Perkins, N.D. and Fuller-Pace, F.V. (2005) The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. EMBO J. Feb 9; 24(3), 543-553.
Perkins, N.D. (2004) NF-kappaB: tumor promoter or suppressor? Trends Cell Biol. Feb; 14(2), 64-69. Review.
Campbell, K.J., Rocha, S. and Perkins, N.D. (2004) Active repression of antiapoptotic gene expression by RelA(p65) NF-kappa B. Mol. Cell. Mar 26; 13(6), 853-865.
Rocha, S., Campbell, K.J. and Perkins, N.D. (2003) p53- and Mdm2-independent repression of NF-kappa B transactivation by the ARF tumor suppressor. Mol. Cell. Jul; 12(1), 15-25.
Rocha, S., Martin, A.M., Meek, D.W. and Perkins, N.D. (2003) p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-kappaB subunit with histone deacetylase 1. Mol. Cell. Biol. Jul; 23(13), 4713-4727.
Girdwood, D., Bumpass, D., Vaughan, O.A., Thain, A., Anderson, L.A., Snowden, A.W., Garcia-Wilson, E., Perkins, N.D. and Hay, R.T. (2003) P300 transcriptional repression is mediated by SUMO modification. Mol. Cell. Apr; 11(4), 1043-1054.