A role for Ubc9 in tumorigenesis - PubMed (original) (raw)
. 2005 Apr 14;24(16):2677-83.
doi: 10.1038/sj.onc.1208210.
Affiliations
- PMID: 15735760
- DOI: 10.1038/sj.onc.1208210
A role for Ubc9 in tumorigenesis
Yin-Yuan Mo et al. Oncogene. 2005.
Abstract
The post-translational modifications ubiquitination and sumoylation have been implicated in regulating many critical cellular pathways. Like ubiquitination, sumoylation is a multistep process involving maturation, activation, conjugation and deconjugation. Ubc9 is a sole E2-conjugating enzyme essential for sumoylation. We have previously shown that alterations of Ubc9 expression affect tumor drug responsiveness. However, it is not clear whether there is any link between sumoylation and tumorigenesis, even though alterations of the ubiquitination pathway can lead to the development of cancer. In this study, we found that Ubc9 expression levels were elevated in ovarian tumors compared to the matched normal ovarian specimens, suggesting that Ubc9 may play a role in tumorigenesis. To test this, we overexpressed a dominant-negative mutant of Ubc9 (Ubc9-DN) and wild-type Ubc9 (Ubc9-WT) in the MCF-7 human breast tumor cells. Inoculating these cells as xenografts in mice revealed that tumors expressing Ubc9-WT grew better than the vector control, while tumors expressing Ubc9-DN exhibited reduced growth. This pattern was also seen in these cells when grown in culture. To better understand the mechanism behind this observation, we profiled gene expressions in these cells by microarray analysis and found alterations in expression of the pro-oncogene bcl-2 in these Ubc9-DN- and Ubc9-WT-expressing cells. Consistent with the bcl-2 results, subsequent studies revealed a higher rate of apoptosis and poor survival for the MCF-7 cells expressing Ubc9-DN, which are associated with downregulation of bcl-2. Together, these results suggest a role for Ubc9 in tumorigenesis at least partially through regulation of bcl-2 expression.
Similar articles
- Methionine adenosyltransferase α2 sumoylation positively regulate Bcl-2 expression in human colon and liver cancer cells.
Tomasi ML, Ryoo M, Ramani K, Tomasi I, Giordano P, Mato JM, Lu SC. Tomasi ML, et al. Oncotarget. 2015 Nov 10;6(35):37706-23. doi: 10.18632/oncotarget.5342. Oncotarget. 2015. PMID: 26416353 Free PMC article. - Regulation of bcl-2 expression by Ubc9.
Lu Z, Wu H, Mo YY. Lu Z, et al. Exp Cell Res. 2006 Jun 10;312(10):1865-75. doi: 10.1016/j.yexcr.2006.02.017. Epub 2006 Mar 29. Exp Cell Res. 2006. PMID: 16566921 - Down-regulation of UBC9 increases the sensitivity of hepatocellular carcinoma to doxorubicin.
Fang S, Qiu J, Wu Z, Bai T, Guo W. Fang S, et al. Oncotarget. 2017 Jul 25;8(30):49783-49795. doi: 10.18632/oncotarget.17939. Oncotarget. 2017. PMID: 28572537 Free PMC article. - Overexpression of a dominant-negative mutant Ubc9 is associated with increased sensitivity to anticancer drugs.
Mo YY, Yu Y, Ee PL, Beck WT. Mo YY, et al. Cancer Res. 2004 Apr 15;64(8):2793-8. doi: 10.1158/0008-5472.can-03-2410. Cancer Res. 2004. PMID: 15087395 - Targeting Ubc9 for cancer therapy.
Mo YY, Moschos SJ. Mo YY, et al. Expert Opin Ther Targets. 2005 Dec;9(6):1203-16. doi: 10.1517/14728222.9.6.1203. Expert Opin Ther Targets. 2005. PMID: 16300471 Review.
Cited by
- Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO.
Reidick C, El Magraoui F, Meyer HE, Stenmark H, Platta HW. Reidick C, et al. Cancers (Basel). 2014 Dec 23;7(1):1-29. doi: 10.3390/cancers7010001. Cancers (Basel). 2014. PMID: 25545884 Free PMC article. Review. - Role of SUMO/Ubc9 in DNA damage repair and tumorigenesis.
Moschos SJ, Mo YY. Moschos SJ, et al. J Mol Histol. 2006 Sep;37(5-7):309-19. doi: 10.1007/s10735-006-9030-0. Epub 2006 Jun 7. J Mol Histol. 2006. PMID: 16758298 - Unconventional protein post-translational modifications: the helmsmen in breast cancer.
Liu J, Wang Q, Kang Y, Xu S, Pang D. Liu J, et al. Cell Biosci. 2022 Feb 25;12(1):22. doi: 10.1186/s13578-022-00756-z. Cell Biosci. 2022. PMID: 35216622 Free PMC article. Review. - Myc-induced SUMOylation is a therapeutic vulnerability for B-cell lymphoma.
Hoellein A, Fallahi M, Schoeffmann S, Steidle S, Schaub FX, Rudelius M, Laitinen I, Nilsson L, Goga A, Peschel C, Nilsson JA, Cleveland JL, Keller U. Hoellein A, et al. Blood. 2014 Sep 25;124(13):2081-90. doi: 10.1182/blood-2014-06-584524. Epub 2014 Aug 20. Blood. 2014. PMID: 25143484 Free PMC article. - Methionine adenosyltransferase α2 sumoylation positively regulate Bcl-2 expression in human colon and liver cancer cells.
Tomasi ML, Ryoo M, Ramani K, Tomasi I, Giordano P, Mato JM, Lu SC. Tomasi ML, et al. Oncotarget. 2015 Nov 10;6(35):37706-23. doi: 10.18632/oncotarget.5342. Oncotarget. 2015. PMID: 26416353 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
- R01 CA102630/CA/NCI NIH HHS/United States
- CA30103/CA/NCI NIH HHS/United States
- CA27469/CA/NCI NIH HHS/United States
- CA102630/CA/NCI NIH HHS/United States
- CA40570/CA/NCI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous