Cancer therapy

Arsenic on the Fingers

Science Signaling  13 Apr 2010:
Vol. 3, Issue 117, pp. ec113
DOI: 10.1126/scisignal.3117ec113

Arsenic, an ancient drug used in traditional Chinese medicine, has attracted wide interest because it has therapeutic activity in patients with acute promyelocytic leukemia (APL). The drug acts by promoting degradation of an oncogenic protein, PML-RARα, a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor α, which is found specifically in APL cells and helps drive their growth. Zhang et al. (see the Perspective by Kogan) now explain how arsenic initiates the molecular events leading to PML-RARα degradation. Arsenic was found to bind directly to cysteine residues within zinc finger domains of PML. Arsenic binding then induced oligomerization of PML, which in turn enhanced its association with an enzyme that helps catalyze SUMOylation, a posttranslational modification that can target proteins for degradation.

X.-W. Zhang, X.-J. Yan, Z.-R. Zhou, F.-F. Yang, Z.-Y. Wu, H.-B. Sun, W.-X. Liang, A.-X. Song, V. Lallemand-Breitenbach, M. Jeanne, Q.-Y. Zhang, H.-Y. Yang, Q.-H. Huang, G.-B. Zhou, J.-H. Tong, Y. Zhang, J.-H. Wu, H.-Y. Hu, H. de Thé, S.-J. Chen, Z. Chen, Arsenic trioxide controls the fate of the PML-RARα oncoprotein by directly binding PML. Science 328, 240–243 (2010). [Abstract] [Full Text]

S. C. Kogan, Poisonous contacts. Science 328, 184–185 (2010). [Summary] [Full Text]