Journal article

Restoration of tumor suppression in prostate cancer by targeting the E3 ligase E6AP

PJ Paul, D Raghu, A-L Chan, T Gulati, L Lambeth, E Takano, MJ Herold, J Hagekyriakou, RL Vessella, C Fedele, M Shackleton, ED Williams, S Fox, S Williams, S Haupt, C Gamell, Y Haupt

ONCOGENE | NATURE PUBLISHING GROUP | Published : 2016

Abstract

Restoration of tumor suppression is an attractive onco-therapeutic approach. It is particularly relevant when a tumor suppressor is excessively degraded by an overactive oncogenic E3 ligase. We previously discovered that the E6-associated protein (E6AP; as classified in the human papilloma virus context) is an E3 ligase that has an important role in the cellular stress response, and it directly targets the tumor-suppressor promyelocytic leukemia protein (PML) for proteasomal degradation. In this study, we have examined the role of the E6AP-PML axis in prostate cancer (PC). We show that knockdown (KD) of E6AP expression attenuates growth of PC cell lines in vitro. We validated this finding in..

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Grants

Awarded by NHMRC


Awarded by CCV grant


Awarded by PCFA grant


Funding Acknowledgements

This work was supported by NHMRC project grants (1049179 and 1063389) and NHMRC Fellowship to YH (9628426), NHMRC project grant to MJH (1049720), PCF creativity grant to SW and YH, CCV grant (1085154), VCA Richard Pratt Fellowship in Prostate Cancer Research to CG, the PCFA grant (NDDA-1811) to EW, Pfizer Australia, NHMRC and Veski foundings to MS, and a prostate initiative grant from the Foundation of the Peter MacCallum Cancer Centre. PrEC line was a generous gift from Dr Patrick Humbert and Helen Pearson at Peter MacCallum Cancer Centre.