Abstract
The region of human chromosome 11p15.5 is linked with Beckwith–Wiedemann syndrome that is associated with susceptibility to Wilms' tumor, rhabdomyosarcoma and hepatoblastoma. TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA; also known as ORCTL2/IMPT1/BWR1A/SLC22A1L) is located in the region. The expression of TSSC5 and other genes in the region is regulated through paternal imprinting. Mutations and/or reduced expression of TSSC5 have been found in certain tumors. TSSC5 encodes an efflux transporter-like protein with 10 transmembrane domains, whose regulation may affect drug sensitivity, cellular metabolism and growth. Here, we present evidences indicating that RING105, a novel conserved RING-finger protein with a PA (protease-associated) domain and a PEST sequence, is a ubiquitin ligase for TSSC5 that can function in concert with the ubiquitin-conjugating enzyme UbcH6. The polyubiquitin target site on TSSC5 was mapped to a region in the 6th hydrophilic loop. Ectopic expression of RING105 in HeLa cells caused an accumulation of cells during G1 that was not observed with the expression of a form of RING105 in which a residue within the RING finger was mutated to inactivate its ligase activity. UbcH6-RING105 may define a novel ubiquitin–proteasome pathway that targets TSSC5 in mammalian cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Albrecht S, Hartmann W, Houshdaran F, Koch A, Gartner B, Prawitt D et al. (2004). Int J Cancer 111: 627–632.
Almond JB, Cohen GM . (2002). Leukemia 16: 433–443.
Biederer T, Volkwein C, Sommer T . (1997). Science 278: 1806–1809.
Bonifacino JS, Weissman AM . (1998). Annu Rev Cell Dev Biol 14: 19–57.
Cooper PR, Smilinich NJ, Day CD, Nowak NJ, Reid LH, Pearsall RS et al. (1998). Genomics 49: 38–51.
Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR, Brandenburg S et al. (2003). Science 299: 1753–1755.
Dao D, Frank D, Qian N, O'Keefe D, Vosatka RJ, Walsh CP et al. (1998). Hum Mol Genet 7: 597–608.
Feinberg AP . (1994). J Cell Sci Suppl 18: 7–12.
Feinberg AP . (1999). Cancer Res 59 (Suppl.): 1743s–1746s.
Gilon T, Chomsky O, Kulka RG . (2000). Mol Cell Biol 20: 7215–7219.
Hampton RY . (2002). Curr Opin Cell Biol 14: 476–482.
Hershko A, Chiechanover A . (1998). Annu Rev Biochem 67: 425–479.
Hershko A . (1997). Curr Opin Cell Biol 9: 788–799.
Hirsch C, Jarosch E, Sommer T, Wolf DH . (2004). Biochim Biophys Acta 1695: 215–223.
Jordan MA, Wilson L . (2004). Nat Rev Cancer 4: 253–265.
Kallio M, Weinstein J, Daum JR, Burke DJ, Gorbsky GJ . (1998). J Cell Biol 141: 1393–1406.
Kallio MJ, Beardmore VA, Weinstein J, Gorbsky GJ . (2002). J Cell Biol 158: 841–847.
Kang D, Chen J, Wong J, Fang G . (2002). J Cell Biol 156: 249–259.
Koi M, Johnson LA, Kalikin LM, Little PF, Nakamura Y, Feinberg AP . (1993). Science 260: 361–364.
Lee MP, Reeves C, Schmitt A, Su K, Connors TD, Hu RJ et al. (1998). Cancer Res 58: 4155–4159.
Lewis A, Murrell A . (2004). Curr Biol 14: R284–R286.
Li TK, Liu LF . (2001). Annu Rev Pharmacol Toxicol 41: 53–77.
Lovering R, Hanson IM, Borden KL, Martin S, O'Reilly NJ, Evan GI et al. (1993). Proc Natl Acad Sci USA 90: 2112–2116.
Mahon P, Bateman A . (2000). Protein Sci 9: 1930–1934.
McCracken AA, Brodsky JL . (2003). Bioessays 25: 868–877.
Pagano M . (1997). FASEB J 11: 1067–1075.
Paulsen M, Davies KR, Bowden LM, Villar AJ, Franck O, Fuermann M et al. (1998). Hum Mol Genet 7: 1149–1159.
Poirier K, Chalas C, Tissier F, Couvert P, Mallet V, Carrie A et al. (2003). J Pathol 201: 473–479.
Ptak C, Gwozd C, Huzil JT, Gwozd TJ, Garen G, Ellison MJ . (2001). Mol Cell Biol 21: 6537–6548.
Ravenel JD, Broman KW, Perlman EJ, Niemitz EL, Jayawardena TM, Bell DW et al. (2001). J Natl Cancer Inst 93: 1698–1703.
Rechsteiner M, Rogers SW . (1996). Trends Biochem Sci 21: 267–271.
Reece M, Prawitt D, Landers J, Kast C, Gros P, Housman D et al. (1998). FEBS Lett 433: 245–250.
Romisch K . (2005). Annu Rev Cell Dev Biol 21: 435–456.
Sagne C, Isambert MF, Henry JP, Gasnier B . (1996). Biochem J 316 (Part 3): 825–831.
Schwienbacher C, Gramantieri L, Scelfo R, Veronese A, Calin GA, Bolondi L et al. (2000). Proc Natl Acad Sci USA 97: 5445–5449.
Schwienbacher C, Sabbioni S, Campi M, Veronese A, Bernardi G, Menegatti A et al. (1998). Proc Natl Acad Sci USA 95: 3873–3878.
Topper LM, Bastians H, Ruderman JV, Gorbsky GJ . (2001). J Cell Biol 154: 707–717.
Acknowledgements
This research is supported by a fellowship from the Breast Cancer Research Program of the US Department of Defense to HY Yamada (DAMD17-02-1-0532), and by a grant from the National Institute of General Medical Science (RO1-GM50412) to GJ Gorbsky. We thank our laboratory members for support, Dr Takumi Kamura (Kyushu University, Japan) for reagents for ubiquitylation assays and Dr Scott Plafker (University of Oklahoma Health Sciences Center) for suggestions.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).
Supplementary information
Rights and permissions
About this article
Cite this article
Yamada, H., Gorbsky, G. Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel ubiquitin ligase RING105. Oncogene 25, 1330–1339 (2006). https://doi.org/10.1038/sj.onc.1209167
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209167
Keywords
This article is cited by
-
Knockdown of Orphan Transporter SLC22A18 Impairs Lipid Metabolism and Increases Invasiveness of HepG2 Cells
Pharmaceutical Research (2019)
-
Silencing SATB1 overcomes temozolomide resistance by downregulating MGMT expression and upregulating SLC22A18 expression in human glioblastoma cells
Cancer Gene Therapy (2018)
-
The ubiquitin-proteasome system and chromosome 17 in cerebellar granule cells and medulloblastoma subgroups
Cellular and Molecular Life Sciences (2017)
-
Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma
Clinical and Translational Oncology (2016)
-
In vitro and in vivo radiosensitization of human glioma U251 cells induced by upregulated expression of SLC22A18
Cancer Gene Therapy (2014)