Poster Presentation 28th Lorne Cancer Conference 2016

E6AP, AN E3 UBIQUITIN LIGASE REGULATES THE TRANSCRIPTION OF CELL CYCLE INHIBITOR, p27 IN PROSTATE CANCER  (#235)

Dinesh Raghu 1 2 , Piotr J. Paul 2 , Ai-Leen Chan 1 , Twishi Gulati 2 , Lambeth Luke 1 , Elena Takano 1 , Stephen Fox 1 , Sue Haupt 1 , Cristina Gamell 1 , Ygal Haupt 1
  1. Peter MacCallum Cancer centre, East Melbourne, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia

Prostate cancer (PC) is one of the most common cancers among men in Australia. E6–associated protein (E6AP), an E3 ubiquitin ligase is involved in the pathogenesis of Human Papilloma Virus (HPV) dependent-cancers1. Recent work from our lab and others provided evidence-associating E6AP with HPV-independent cancers2 including PC3. The p27 protein is a negative regulator of the cell cycle and expressed at low levels in cancers including PC leading to poor prognosis4. Further, p27 was found to be negatively regulated by E6AP in a neuron cell line5. We therefore hypothesized that p27 is targeted by E6AP in PC. To elucidate the role of E6AP in regulating p27 in PC we have knocked down (KD) E6AP in PC cell lines and found an up-regulation in expression of mRNA and protein of p27 in vitro and in vivo. Importantly, our findings are supported by an inverse correlation between the expression of E6AP and p27 in PC using a tissue microarray. Data will be presented on our current thoughts of the molecular mechanism underlying the regulation of p27 by E6AP in PC cells.

1.     A. L. Talis, J. M. Huibregtse and P. M. Howley, The Journal of biological chemistry, 1998, 273, 6439-6445.

2.     K. Wolyniec, J. Shortt, E. de Stanchina, Y. Levav-Cohen, O. Alsheich-Bartok, I. Louria-Hayon, V. Corneille, B. Kumar, S. J. Woods, S. Opat, R. W. Johnstone, C. L. Scott, D. Segal, P. P. Pandolfi, S. Fox, A. Strasser, Y. H. Jiang, S. W. Lowe, S. Haupt and Y. Haupt, Blood, 2012, 120, 822-832.

3.     S. E. Birch, J. G. Kench, E. Takano, P. Chan, A. L. Chan, K. Chiam, A. S. Veillard, P. Stricker, S. Haupt, Y. Haupt, L. Horvath and S. B. Fox, Annals of oncology, 2014.

4.     I. M. Chu, L. Hengst and J. M. Slingerland, Nature reviews. Cancer, 2008, 8, 253-267.

5.     A. Mishra, S. K. Godavarthi and N. R. Jana, Neurobiology of disease, 2009, 36, 26-34.