DOI QR코드

DOI QR Code

Inhibition of the NEDD8 Conjugation Pathway by shRNA to UBA3, the Subunit of the NEDD8-Activating Enzyme, Suppresses the Growth of Melanoma Cells

  • Cheng, Fang (Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Chen, Hao (Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Zhang, Lei (Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Ruo-Hong, Li (Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Liu, Yi (Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Sun, Jian-Fang (Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College)
  • 발행 : 2012.01.31

초록

Neural precursor cell-expressed developmentally down-regulated 8 (NEDD8), a ubiquitin-like protein, mainly functions through covalent ligation to cullin proteins. Conjugation of NEDD8 with cullins can promote ubiquitination, which plays a critical role in the degradation of many proteins. UBA3 is the subunit of NEDD8-activating enzyme which is one of the keys for NEDD8 linkage to cullin proteins. Previous research showed NEDD8 conjugation to be up-regulated in highly proliferative cell lines. In the present study, up-regulated NEDD8 conjugation was observed in melanoma cell lines by Western blot analysis. After down-regulation with a RNAi to UBA3, proliferation of M14 was suppressed in vitro and in vivo. In conclusion, up-regulated NEDD8 conjugation may be involved in the development of melanoma. Interference in this pathway might offera promising method for melanoma therapy.

키워드

참고문헌

  1. Allende-Vega N, Saville MK (2010). Targeting the ubiquitinproteasome system to activate wild-type p53 for cancer therapy. Semin Cancer Biol, 20, 29-39. https://doi.org/10.1016/j.semcancer.2009.10.004
  2. Brownell JE, Sintchak MD, Gavin JM, et al (2010). Substrateassisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Mol Cell, 37, 102-11. https://doi.org/10.1016/j.molcel.2009.12.024
  3. Chairatvit K, Ngamkitidechakul C (2007). Control of cell proliferation via elevated NEDD8 conjugation in oral squamous cell carcinoma. Mol Cell Biochem, 306, 163-9. https://doi.org/10.1007/s11010-007-9566-7
  4. Croghan GA, Suman VJ, Maples WJ, et al (2010). A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma: a phase 2 consortium study. Cancer, 116, 3463-8. https://doi.org/10.1002/cncr.25191
  5. Dace A, Zhao L, Park KS, et al (2000). Hormone binding induces rapid proteasome-mediated degradation of thyroid hormone receptors. Proc Natl Acad Sci U S A, 97, 8985-90. https://doi.org/10.1073/pnas.160257997
  6. Demo SD, Kirk CJ, Aujay MA, et al (2007). Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res, 67, 6383-91. https://doi.org/10.1158/0008-5472.CAN-06-4086
  7. Germain D (2011). Skp2 and Skp2B team up against Rb and p53. Cell Div, 6, 1. https://doi.org/10.1186/1747-1028-6-1
  8. Glinsky GV, Glinsky VV, et al (1996). Apoptosis amd metastasis: a superior resistance of metastatic cancer cells to programmed cell death. Cancer Lett, 101, 43-51. https://doi.org/10.1016/0304-3835(96)04112-2
  9. Gong L, Yeh ET (1999). Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem, 274, 12036-42. https://doi.org/10.1074/jbc.274.17.12036
  10. Hershko A (2005). The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle. Cell Death Differ, 12, 1191-7. https://doi.org/10.1038/sj.cdd.4401702
  11. Hjerpe R, Rodríguez MS (2008). Alternative UPS drug targets upstream the 26S proteasome. Int J Biochem Cell Biol, 40, 1126-40. https://doi.org/10.1016/j.biocel.2007.11.021
  12. Huang DT, Ayrault O, Hunt HW, et al (2009). E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol Cell, 33, 483-95. https://doi.org/10.1016/j.molcel.2009.01.011
  13. Kamitani T, Kito K, Nguyen HP, et al (1997). Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein. J Biol Chem, 272, 28557-62. https://doi.org/10.1074/jbc.272.45.28557
  14. Lin JJ, Milhollen MA, Smith PG, et al (2010). NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer Res, 70, 10310-20. https://doi.org/10.1158/0008-5472.CAN-10-2062
  15. O'Connor OA (2005). Marked clinical activity of the proteasome inhibitor bortezomib in patients with follicular and mantlecell lymphoma. Clin Lymphoma Myeloma, 6, 191-9. https://doi.org/10.3816/CLM.2005.n.046
  16. Rabut G, Peter M (2008). Function and regulation of protein neddylation. 'Protein modifications: beyond the usual suspects' review series. EMBO, 9, 969-76. https://doi.org/10.1038/embor.2008.183
  17. Soucy TA, Smith PG, Milhollen MA, et al (2009). An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature, 458, 732-6. https://doi.org/10.1038/nature07884
  18. Tsvetkov P, Reuven N, Shaul Y (2010). Ubiquitin-independent p53 proteasomal degradation. Cell Death Differ, 17, 103-7. https://doi.org/10.1038/cdd.2009.67
  19. Wada H, Yeh ET, Kamitani T (2000). A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo. J Biol Chem, 275, 17008-15. https://doi.org/10.1074/jbc.275.22.17008
  20. Wu K, Chen A, Pan ZQ (2000). Conjugation of Nedd8 to CUL1 enhances the ability of the ROC1-CUL1 complex to promote ubiquitin polymerization. J Biol Chem, 275, 32317-24. https://doi.org/10.1074/jbc.M004847200
  21. Xirodimas DP, Scheffner M (2010). Ubiquitin family members in the regulation of the tumor suppressor p53. Subcell Biochem, 54, 116-35. https://doi.org/10.1007/978-1-4419-6676-6_10
  22. Yu ZK, Gervais JL, Zhang H (1998). Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21 (CIP1/ WAF1) and cyclin D proteins. Proc Natl Acad Sci U S A, 95, 11324-9. https://doi.org/10.1073/pnas.95.19.11324

피인용 문헌

  1. Expression of neddylation-related proteins in melanoma cell lines and the effect of neddylation on melanoma proliferation vol.7, pp.5, 2014, https://doi.org/10.3892/ol.2014.1953