Mutant protein in tumors hits the DEK

Abstract

Cancer genome sequencing projects have uncovered a multitude of mutations in human tumors. Understanding whether and how these mutations contribute to tumor development and progression could ultimately lead to new therapies. Theurillat et al. studied SPOP, the protein product of a gene that is recurrently mutated in prostate cancer. Normally, SPOP helps attach ubiquitin to proteins, tagging them for degradation. The new work shows that the tumor-associated mutant SPOP loses this tagging ability, which results in the stabilization of specific proteins that would otherwise be degraded. One of the most intriguing of these proteins was DEK, which helps prostate cancer cells invade into surrounding tissue. J.-P. P. Theurillat, N. D. Udeshi, W. J. Errington, T. Svinkina, S. C. Baca, M. Pop, P. J. Wild, M. Blattner, A. C. Groner, M. A. Rubin, H. Moch, G. G. Prive, S. A. Carr, L. A. Garraway, Ubiquitylome analysis identifies dysregulation of effector substrates in SPOP-mutant prostate cancer. Science346, 85–89 (2014). [Abstract][Full Text]