Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
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)
  • Published : 2012.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

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.

Keywords

References

  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

Cited by

  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