oncogenic retroviridae proteins


Summary: Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.

Top Publications

  1. Duan L, Miura Y, Dimri M, Majumder B, Dodge I, Reddi A, et al. Cbl-mediated ubiquitinylation is required for lysosomal sorting of epidermal growth factor receptor but is dispensable for endocytosis. J Biol Chem. 2003;278:28950-60 pubmed
  2. Kochva U, Leonov H, Arkin I. Modeling the structure of the respiratory syncytial virus small hydrophobic protein by silent-mutation analysis of global searching molecular dynamics. Protein Sci. 2003;12:2668-74 pubmed
    ..The model of the structure obtained is a channel-like homopentamer whose minimal transmembrane pore diameter is 1.46 A. ..
  3. Diehl J, McKinsey T, Hannink M. Differential pp40I kappa B-beta inhibition of DNA binding by rel proteins. Mol Cell Biol. 1993;13:1769-78 pubmed
    ..These results demonstrate the presence of an interaction between internal and C-terminal regions of the c-rel protein that is important for the ability of c-rel to regulate the proliferation of lymphoid cells. ..
  4. Fuentes S, Tran K, Luthra P, Teng M, He B. Function of the respiratory syncytial virus small hydrophobic protein. J Virol. 2007;81:8361-6 pubmed publisher
    ..The results indicate that the SH protein of RSV has a function similar to that of PIV5 SH and that it can inhibit TNF-alpha signaling...
  5. Donaldson J, Dempsey P, Reddy S, Bouton A, Coffey R, Hanks S. Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells. Exp Cell Res. 2000;256:168-78 pubmed
    ..Our findings provide novel insight into the normal cellular activities regulated by both Cas and nephrocystin, and raise the possibility that these proteins have a related function in polarized epithelial cells. ..
  6. Carrasco D, Rizzo C, Dorfman K, Bravo R. The v-rel oncogene promotes malignant T-cell leukemia/lymphoma in transgenic mice. EMBO J. 1996;15:3640-50 pubmed
    ..These v-Rel mice should aid in the study of lymphoma development, T-cell development and NF-kappa B regulation. ..
  7. Harte M, Hildebrand J, Burnham M, Bouton A, Parsons J. p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase. J Biol Chem. 1996;271:13649-55 pubmed
    ..The association of p130(Cas) with pp125(FAK), a kinase which is activated upon cell adhesion, is likely to be functionally important in integrin mediated signal transduction. ..
  8. Gan S, Ng L, Lin X, Gong X, Torres J. Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain. Protein Sci. 2008;17:813-20 pubmed publisher
    ..We provide a model for this pore, which should be useful in mutagenesis studies to elucidate its role during the virus cycle. ..
  9. Gilmore T. Role of rel family genes in normal and malignant lymphoid cell growth. Cancer Surv. 1992;15:69-87 pubmed
    ..In addition, rel proteins are likely to be involved in T cell diseases caused by the human retroviruses HTLV-I and HIV-1. Therefore, rel proteins could serve as targets for anti-viral or anti-cancer therapies. ..

More Information


  1. Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Mano H, et al. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. EMBO J. 1994;13:3748-56 pubmed
  2. Verma I, Stevenson J, Schwarz E, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35 pubmed
  3. Gilmore T. Malignant transformation by mutant Rel proteins. Trends Genet. 1991;7:318-22 pubmed
    ..Nevertheless, there is still much to be learned about their precise mechanism of action, including the process by which the original member of this family, v-Rel, malignantly transforms cells. ..
  4. Zhu K, Debreceni B, Li R, Zheng Y. Identification of Rho GTPase-dependent sites in the Dbl homology domain of oncogenic Dbl that are required for transformation. J Biol Chem. 2000;275:25993-6001 pubmed
  5. Tran Quang C, Gautreau A, Arpin M, Treisman R. Ezrin function is required for ROCK-mediated fibroblast transformation by the Net and Dbl oncogenes. EMBO J. 2000;19:4565-76 pubmed
    ..These results implicate ROCK-mediated ezrin C-terminal phosphorylation in transformation by RhoGEFs. ..
  6. Brenner B, Kadel S, Birle A, Linderkamp O. L-selectin tyrosine phosphorylates cbl and induces association of tyrosine-phosphorylated cbl with crkl and grb2. Biochem Biophys Res Commun. 2001;282:41-7 pubmed
    ..Therefore, the adapter protein Cbl plays a role in L-selectin signaling and might modulate immune function by the specific recruitment of signaling molecules to multiprotein complexes. ..
  7. Luo H, Wan X, Wu Y, Wu J. Cross-linking of EphB6 resulting in signal transduction and apoptosis in Jurkat cells. J Immunol. 2001;167:1362-70 pubmed
    ..Our results show that EphB6 has important functions in T cells, and it can transduce signals into the cells via proteins it associates with. ..
  8. Moynet D, Pouliquen J, Londos Gagliardi D, Buigues R, Moreau J, Bedjabaga I, et al. High variability of HTLV-I in a remote population of Gabon as compared to that of a similar population of French Guiana. Virus Genes. 2001;23:257-61 pubmed
    ..We found a much higher degree of gp46 surface envelope glycoprotein sequence conservation in the Guianese village than in the Gabonese one. ..
  9. Yugawa T, Amanuma H. Pathogenicity of a mutant friend spleen focus-forming virus encoding an Env-like membrane glycoprotein (gp55) with substitution by a xenotropic murine leukemia virus Env gp70 sequence. Microbiol Immunol. 1998;42:335-9 pubmed
    ..XE gp55 displayed almost the same biological activities as the wild-type gp55, excluding the above possibility...
  10. Alevizopoulos A, Mermod N. Antagonistic regulation of a proline-rich transcription factor by transforming growth factor beta and tumor necrosis factor alpha. J Biol Chem. 1996;271:29672-81 pubmed
    ..These results identify CTF-1 as a molecular target of mutually antagonistic TGF-beta and TNF-alpha regulation, and they further suggest a molecular mechanism for the opposing effects of these growth factors on gene expression. ..
  11. Marshall M. Interactions between Ras and Raf: key regulatory proteins in cellular transformation. Mol Reprod Dev. 1995;42:493-9 pubmed
    ..Phosphorylation of c-Raf-1 serine 43 is believed to cause an N-terminal cap structure to cover the Ras docking site. ..
  12. Cosgaya J, Aranda A. Ras- and Raf-mediated regulation of transforming growth factor beta 1 gene expression by ligands of tyrosine kinase receptors in PC12 cells. Oncogene. 1996;12:2651-60 pubmed
    ..These results suggest that during proliferation or growth factor-induced differentiation of sympathetic neurons there is an increase in TGF-beta1 that could be an important mediator of neural cells function. ..
  13. Susova O, Gurtsevich V. [The role of region pX in the life cycle of HTLV-I and in carcinogenesis]. Mol Biol (Mosk). 2003;37:392-403 pubmed
    ..Tax functions are described, including transcriptional trans-activation, trans-repression, and effects on apoptosis and the cell cycle. The roles of Tax and Rex in controlling gene expression and replication of HTLV-I are discussed. ..
  14. Veazey R, Lifson J, Schmitz J, Kuroda M, Piatak M, Pandrea I, et al. Dynamics of Simian immunodeficiency virus-specific cytotoxic T-cell responses in tissues. J Med Primatol. 2003;32:194-200 pubmed
  15. Duval M, B├ędard Goulet S, Delisle C, Gratton J. Vascular endothelial growth factor-dependent down-regulation of Flk-1/KDR involves Cbl-mediated ubiquitination. Consequences on nitric oxide production from endothelial cells. J Biol Chem. 2003;278:20091-7 pubmed
    ..Cbl thus plays a role in the regulation of VEGF signaling by mediating the stimulated ubiquitination and, consequently, degradation of Flk-1 in endothelial cells. ..
  16. Van Rompay K, Abel K, Lawson J, Singh R, Schmidt K, Evans T, et al. Attenuated poxvirus-based simian immunodeficiency virus (SIV) vaccines given in infancy partially protect infant and juvenile macaques against repeated oral challenge with virulent SIV. J Acquir Immune Defic Syndr. 2005;38:124-34 pubmed
    ..The results of these investigations suggest that immunization of human infants with poxvirus-based HIV vaccine candidates may offer protection against early and late HIV infection through breastfeeding. ..
  17. Kralova J, Liss A, Bargmann W, Bose H. AP-1 factors play an important role in transformation induced by the v-rel oncogene. Mol Cell Biol. 1998;18:2997-3009 pubmed
    ..This is the first report showing that v-Rel might execute its oncogenic potential through modulating the activity of early response genes. ..
  18. Whitehead I, Khosravi Far R, Kirk H, Trigo Gonzalez G, Der C, Kay R. Expression cloning of lsc, a novel oncogene with structural similarities to the Dbl family of guanine nucleotide exchange factors. J Biol Chem. 1996;271:18643-50 pubmed
    ..Lsc is a member of a growing family of proteins that may function as activators of Rho family GTPases in a developmental or tissue-specific manner. ..
  19. Rubino D, Driggers P, Arbit D, Kemp L, Miller B, Coso O, et al. Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action. Oncogene. 1998;16:2513-26 pubmed
    ..Taken together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone receptors. ..
  20. Kieser A, Seitz T, Adler H, Coffer P, Kremmer E, Crespo P, et al. Protein kinase C-zeta reverts v-raf transformation of NIH-3T3 cells. Genes Dev. 1996;10:1455-66 pubmed
    ..In summary, our data suggest that PKC-zeta counteracts v-raf transformation by modulating the expression of the transcription factors junB and egr-1. ..
  21. Lee R, Gillet G, Burnside J, Thomas S, Neiman P. Role of Nr13 in regulation of programmed cell death in the bursa of Fabricius. Genes Dev. 1999;13:718-28 pubmed
    ..Bursal transplantation studies demonstrated that Nr13 could prevent the in vivo programmed elimination of bursal stem cells after hatching, suggesting that Nr13 plays a role in maintaining bursal stem cells...
  22. Sagara Y, Inoue Y, Sagara Y, Kashiwagi S. Involvement of molecular mimicry between human T-cell leukemia virus type 1 gp46 and osteoprotegerin in induction of hypercalcemia. Cancer Sci. 2009;100:490-6 pubmed publisher
    ..Improvement by OPG in the adverse effect indicates that the central region of HTLV-1 Gp46 acts as an antagonist for OPG and leads to hypercalcemia. ..
  23. Oka M, Nagai H, Ando H, Fukunaga M, Matsumura M, Araki K, et al. Regulation of melanogenesis through phosphatidylinositol 3-kinase-Akt pathway in human G361 melanoma cells. J Invest Dermatol. 2000;115:699-703 pubmed
    ..These results indicate that phosphatidylinositol 3-kinase regulates melanogenesis by modulating the expression of tyrosinase, and that activation of Akt is sufficient for suppression of melanin production in G361 melanoma cells. ..
  24. Vanni C, Parodi A, Mancini P, Visco V, Ottaviano C, Torrisi M, et al. Phosphorylation-independent membrane relocalization of ezrin following association with Dbl in vivo. Oncogene. 2004;23:4098-106 pubmed
    ..These results indicate that Dbl could induce translocation of ezrin to the plasma membrane through a mechanism that does not require ezrin C-terminus phosphorylation by Rho-associated kinases. ..
  25. Rice J, Buchan S, Stevenson F. Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen. J Immunol. 2002;169:3908-13 pubmed
    ..These data demonstrate the power of epitope-specific CTL against tumor cells and illustrate a strategy for priming immunity via a dual component DNA vaccine. ..
  26. Hamilton V, Stone D, Pritchard S, Cantor G. Bovine leukemia virus gp30 transmembrane (TM) protein is not tyrosine phosphorylated: examining potential interactions with host tyrosine-mediated signaling. Virus Res. 2002;90:155-69 pubmed
    ..Thus BLV TM is not likely to modify host signal pathways through interactions between phosphorylated tyrosines of the ITAM or ITIM motifs and host-cell tyrosine kinases or phosphatases. ..
  27. Oomens A, Megaw A, Wertz G. Infectivity of a human respiratory syncytial virus lacking the SH, G, and F proteins is efficiently mediated by the vesicular stomatitis virus G protein. J Virol. 2003;77:3785-98 pubmed
    ..This is the first report of the recovery of an infectious HRSV lacking a fusion protein of the Paramyxoviridae family and of manipulation of the HRSV entry pathway via incorporation of a nonparamyxoviral transmembrane glycoprotein. ..
  28. White D, Gilmore T. Temperature-sensitive transforming mutants of the v-rel oncogene. J Virol. 1993;67:6876-81 pubmed
    ..5 degrees C but rapidly senesced at 41.5 degrees C. Both mutant v-Rel proteins were also ts for DNA binding in vitro. These mutants may be valuable for identifying genes directly regulated by v-rel. ..
  29. Kiyokawa E, Hashimoto Y, Kurata T, Sugimura H, Matsuda M. Evidence that DOCK180 up-regulates signals from the CrkII-p130(Cas) complex. J Biol Chem. 1998;273:24479-84 pubmed
    ..These findings suggest that DOCK180 positively regulates signaling from integrins to CrkII-p130(Cas) complexes at focal adhesions. ..
  30. You M, Ku P, Hrdlickova R, Bose H. ch-IAP1, a member of the inhibitor-of-apoptosis protein family, is a mediator of the antiapoptotic activity of the v-Rel oncoprotein. Mol Cell Biol. 1997;17:7328-41 pubmed
    ..Collectively, these results suggest that ch-IAP1 is induced during the v-Rel-mediated transformation process and functions as a suppressor of apoptosis in v-Rel-transformed cells. ..
  31. Belec L, Georges Courbot M, Georges A, Mohamed A, Londos Gagliardi D, Hallouin M, et al. Cervicovaginal synthesis of IgG antibodies to the immunodominant 175-199 domain of the surface glycoprotein gp46 of human T-cell leukemia virus type I. J Med Virol. 1996;50:42-9 pubmed
    ..Since anti-gp46/175-Pro-199 antibodies usually support reactivities to neutralizing domains, their presence could be relevant for limiting HTLV-I transmission via cervicovaginal secretions. ..
  32. Stancato L, Chow Y, Hutchison K, Perdew G, Jove R, Pratt W. Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a cell-free system. J Biol Chem. 1993;268:21711-6 pubmed
  33. Hagemeier C, Bannister A, Cook A, Kouzarides T. The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proc Natl Acad Sci U S A. 1993;90:1580-4 pubmed
    ..The potential for RB to influence transcription by using TFIID- and TFIIB-related functions is discussed. ..
  34. Joseph R, Norris F. Substrate specificity and recognition is conferred by the pleckstrin homology domain of the Dbl family guanine nucleotide exchange factor P-Rex2. J Biol Chem. 2005;280:27508-12 pubmed
    ..Thus substrate recognition can now be added to the growing list of functions that are being attributed to the PH domain of Dbl family GEFs. ..
  35. Hwang S, Jung J, Lim S, Kim J, Kim T, Cho K, et al. LY294002 inhibits interferon-gamma-stimulated inducible nitric oxide synthase expression in BV2 microglial cells. Biochem Biophys Res Commun. 2004;318:691-7 pubmed
  36. Lipsick J, Wang D. Transformation by v-Myb. Oncogene. 1999;18:3047-55 pubmed
    ..The E26 leukemia virus was first described in the 1960s and causes an acute erythroblastosis in chickens, more reminiscent of the disease caused by avian erythroblastosis virus (AEV) than by AMV (Ivanov et al., 1962)...
  37. van Leeuwen J, Paik P, Samelson L. Activation of nuclear factor of activated T cells-(NFAT) and activating protein 1 (AP-1) by oncogenic 70Z Cbl requires an intact phosphotyrosine binding domain but not Crk(L) or p85 phosphatidylinositol 3-kinase association. J Biol Chem. 1999;274:5153-62 pubmed
    ..We hypothesize that 70Z Cbl acts as a dominant negative by blocking the negative regulatory function of the Cbl phosphotyrosine binding domain on protein-tyrosine kinases. ..
  38. McCarty J. The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events. Bioessays. 1998;20:913-21 pubmed
    ..Various data are discussed which collectively support a role for Nck in the regulation of multiple intracellular signaling events. ..
  39. Czernik P, Peterson C, Hurlburt B. Preferential binding of MyoD-E12 versus myogenin-E12 to the murine sarcoma virus enhancer in vitro. J Biol Chem. 1996;271:9141-9 pubmed
    ..Interestingly, MyoD-E12 bound all of the individual E-boxes tested with positive cooperativity indicating DNA-mediated dimerization of the protein subunits. ..
  40. Seroussi E, Kedra D, Kost Alimova M, Sandberg Nordqvist A, Fransson I, Jacobs J, et al. TOM1 genes map to human chromosome 22q13.1 and mouse chromosome 8C1 and encode proteins similar to the endosomal proteins HGS and STAM. Genomics. 1999;57:380-8 pubmed
    ..Using a genomic PAC clone, we demonstrate that the mouse Tom1 and Hmox1 genes are part of an as yet undescribed syntenic group between mouse chromosome 8C1 and human chromosome 22q13.1. ..
  41. Hofmann Lehmann R, Cattori V, Tandon R, Boretti F, Meli M, Riond B, et al. Vaccination against the feline leukaemia virus: outcome and response categories and long-term follow-up. Vaccine. 2007;25:5531-9 pubmed
    ..Persistence of plasma viral RNA was moderately associated with reactivation of FeLV infection. In conclusion, sensitive molecular assays are important tools for reviewing pathogenesis of FeLV infection. ..
  42. Hromas R, May W, Denny C, Raskind W, Moore J, Maki R, et al. Human FLI-1 localizes to chromosome 11Q24 and has an aberrant transcript in neuroepithelioma. Biochim Biophys Acta. 1993;1172:155-8 pubmed
    ..In the neuroepithelioma cell line TC-32 the FLI-1 transcript is present but has an aberrant structure, indicating that it may be rearranged in neuroepithelioma. ..
  43. Vasko V, Saji M, Hardy E, Kruhlak M, Larin A, Savchenko V, et al. Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer. J Med Genet. 2004;41:161-70 pubmed
    ..Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition. These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression. ..
  44. Owczarek C, Portbury K, Hardy M, O Leary D, Kudoh J, Shibuya K, et al. Detailed mapping of the ERG-ETS2 interval of human chromosome 21 and comparison with the region of conserved synteny on mouse chromosome 16. Gene. 2004;324:65-77 pubmed
    ..Our studies have important implications for Down syndrome as this region contains multiple mRNA transcripts, both coding and potentially noncoding, that may play as yet undescribed roles in the pathogenesis of this disorder. ..
  45. Okazaki M, Kishida S, Murai H, Hinoi T, Kikuchi A. Ras-interacting domain of Ral GDP dissociation stimulator like (RGL) reverses v-Ras-induced transformation and Raf-1 activation in NIH3T3 cells. Cancer Res. 1996;56:2387-92 pubmed
  46. Pelchen Matthews A, Kramer B, Marsh M. Infectious HIV-1 assembles in late endosomes in primary macrophages. J Cell Biol. 2003;162:443-55 pubmed
    ..This notion has significant implications for understanding the biology of HIV and its cell-cell transmission. ..
  47. Smith S, de Lange T. TRF1, a mammalian telomeric protein. Trends Genet. 1997;13:21-6 pubmed
    ..The recent isolation of TRF1, the mammalian telomeric-repeat binding factor, should now allow the structure and function of the telomeric complex to be examined in detail. ..
  48. Guerrero C, Fernandez Medarde A, Rojas J, Font de Mora J, Esteban L, Santos E. Transformation suppressor activity of C3G is independent of its CDC25-homology domain. Oncogene. 1998;16:613-24 pubmed
    ..Our results suggest that the N-terminal region of C3G, and not its catalytic domain, may be responsible for the inhibitory effects observed. ..
  49. Orvell C, Kalantari M, Johansson B. Characterization of five conserved genotypes of the mumps virus small hydrophobic (SH) protein gene. J Gen Virol. 1997;78 ( Pt 1):91-5 pubmed
    ..Different genotypes can circulate simultaneously in a given geographical location. In Stockholm, genotypes A and D or C and D were found over different time periods. In contrast, only genotype B was found in Japan. ..
  50. Ye J, Silverman L, Lairmore M, Green P. HTLV-1 Rex is required for viral spread and persistence in vivo but is dispensable for cellular immortalization in vitro. Blood. 2003;102:3963-9 pubmed
    ..However, Rex is critical for efficient infection of cells and persistence in vivo. ..
  51. Wilson K, Maerz A, Poumbourios P. Evidence that the transmembrane domain proximal region of the human T-cell leukemia virus type 1 fusion glycoprotein gp21 has distinct roles in the prefusion and fusion-activated states. J Biol Chem. 2001;276:49466-75 pubmed
  52. Esteban E, Sherman M, Poiesz B, Marshak R, Waters D, Ferrer J. Transmission of human T cell leukemia virus type I to sheep: antibody profile and detection of viral DNA sequences. AIDS Res Hum Retroviruses. 1996;12:1717-24 pubmed
    ..None of the sheep showed clinical abnormalities during the observation period. The potential value of the sheep model for studying atypical virus-host interactions in infected people is discussed. ..
  53. Wertheim J, Worobey M. A challenge to the ancient origin of SIVagm based on African green monkey mitochondrial genomes. PLoS Pathog. 2007;3:e95 pubmed
    ..This study substantially weakens the theory of ancient SIV infection followed by codivergence with its primate hosts. ..