Salinosporamides A and B Inhibit Proteasome Activity and Delay the Degradation of N-end Rule Model Substrates

다국어 초록 (Multilingual Abstract)

The proteasome, which is highly evolutionarily conserved, is responsible for the degradation of most shortlived proteins in cells. Small-molecule inhibitors targeting the proteasome's degradative activity have been extensively developed as lead compounds for various human diseases. An exemplified molecule is bortezomib, which was approved by FDA in 2003 for the treatment of multiple myeloma. Here, using transiently and stably expressed N-end rule model substrates in mammalian cells, we evaluated and identified that salinosporamide A and salinosporamide B effectively inhibited the proteasomal degradation. Considering that a variety of proteasome substrates are implicated in the pathogenesis of many diseases, they have the potential to be clinically applicable as therapeutic agents.

참고문헌 (Reference)

1 Coux, O, 65 : 801-, 1996

2 Lee, M. J, 105 : 100-, 2008

3 Cardozo, C, 47 : 296-, 1993

4 Orlowski, M, 32 : 1563-, 1993

5 Ishizawa, J, 25 : 697-, 2004

6 Santer, F. R, 66 : 3024-, 2006

7 Brooks, A. D, 1059 : 160-, 2005

8 Inoue, T, 17 : 261-, 2006

9 Drexler, H. C, 94 : 855-, 1997

10 Pagano, M, 11 : 1067-, 1997

11 Adams, J, 59 : 2615-, 1999

12 Adams, J, 4 : 349-, 2004

13 Chauhan, D, 45 : 465-, 2005

14 Feling, R. H, 42 : 355-, 2003

15 Lee, M. J, R110.00387-, 2011

16 Chauhan, D, 8 : 407-, 2005

17 Hamilton, A. L., 23 : 6107-, 2005

18 Groll, M, 128 : 5136-, 2006

19 Lee, M. J., 102 : 15030-, 2005

20 Lee, M. J, 287 : 24043-, 2012

21 Kisselev, A. F, "A. L. J. Biol. Chem. 2006" 281 : 8582-, 2006