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First published online 6 May 2008
doi: 10.1242/jcs.020552

Journal of Cell Science 121, 1825-1831 (2008)
Published by The Company of Biologists 2008
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Research Article

UV-induced degradation of securin is mediated by SKP1-CUL1-βTrCP E3 ubiquitin ligase

M. Cristina Limón-Mortés1, Mar Mora-Santos1, Águeda Espina2, José A. Pintor-Toro2, Antonio López-Román1, María Tortolero1 and Francisco Romero1,*

1 Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, Apdo 1095, 41080 Sevilla, Spain
2 Centro Andaluz de Biología y Medicina Regenerativa, CSIC, Sevilla, Spain

* Author for correspondence (e-mail: frport{at}us.es)

Accepted 11 March 2008

Securin is a chaperone protein with bifunctional properties. It binds to separase to inhibit premature sister chromatid separation until the onset of anaphase, and it also takes part in cell-cycle arrest after UV irradiation. At metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome (APC/C), allowing activation of separase. However, although securin is reported to undergo proteasome-dependent degradation after UV irradiation, the ubiquitin ligase responsible for securin ubiquitylation has not been well characterized. In this study, we show that UV radiation induced a marked reduction of securin in both the nucleus and cytoplasm. Moreover, we show that GSK-3β inhibitors prevent securin degradation, and that CUL1 and βTrCP are involved in this depletion. We also confirmed that SKP1-CUL1-βTrCP (SCFβTrCP) ubiquitylates securin in vivo, and identified a conserved and unconventional βTrCP recognition motif (DDAYPE) in the securin primary amino acid sequence of humans, nonhuman primates and rodents. Furthermore, downregulation of βTrCP caused an accumulation of securin in non-irradiated cells. We conclude that SCFβTrCP is the E3 ubiquitin ligase responsible for securin degradation after UV irradiation, and that it is involved in securin turnover in nonstressed cells.

Key words: Cell cycle, Degradation, Proteasome, Securin, Ubiquitylation, Ultraviolet radiation






© The Company of Biologists Ltd 2008