Triad 1 induces apoptosis by p53 activation

Edited by Varda Rotter

Received 13 December 2009; received in revised form 2 March 2010; accepted 7 March 2010. published online 10 March 2010.

Abstract

Triad 1 (2 RING [really interesting new gene] fingers and DRIL [double RING finger linked] 1) is an E3 ligase that induces apoptosis and clonogenic inhibition in myeloid cells through Gfi-1 stabilization. Here we demonstrate that Triad 1 induces apoptosis in several cancer cell lines including MCF7, A549, U2OS, and HCT 116 p53+/+ cells via its RING ligase activity. Interestingly, in these cancer cells, Triad 1-induced apoptosis is not mediated by Gfi-1 stabilization but is instead p53-dependent. Moreover, Triad 1 promotes transactivation of p53. These results suggest that Triad 1 can induce apoptosis through its ligase activity via p53 activation.

Abbreviations: RING, really interesting new gene, DRIL, double RING finger linked

Keywords: Triad 1, Gfi-1, Apoptosis, p53, RING finger

a Functional Genome Research Institute, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea

b Department of Chemistry, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea

c Laboratory of Functional Genomics, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Republic of Korea

d Division of Radiation Effect Research, Radiation Health Research Institute of KHNP, 388-1 Ssangmoon-dong, Dongbong-gu, Seoul 132-703, Republic of Korea

e LIFEnGENE, Inc., Venture Business Supporting Center, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea

Corresponding author. Fax: +82 2 3437 4055.

Corresponding author. Address: Functional Genome Research Institute, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea. Fax: +82 2 3437 4055.

1 These authors contributed equally to this work.

PII: S0014-5793(10)00205-X

doi:10.1016/j.febslet.2010.03.011

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