Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Identification of E2F-3B, an alternative form of E2F-3 lacking a conserved N-terminal region

Oncogene volume 19, pages 3422–3433 (2000)Cite this article

Abstract

We have identified a novel form of the full-length E2F-3 protein that we term E2F-3B. In contrast to full-length E2F-3, which is expressed only at the G1/S boundary, E2F-3B is detected throughout the cell cycle with peak levels in G0 where it is associated with Rb. Transfection and in vitro translation experiments demonstrate that a protein identical to E2F-3B in size and iso-electric point is produced from the E2F-3 mRNA via the use of an alternative translational start site. This alternative initiation codon was mapped by mutagenesis to codon 102, an ACG codon. Mutation of the ACG codon at position 102 abolished E2F-3B expression, whereas the conversion of ACG 102 to a consensus ATG led to the expression of a protein indistinguishable from E2F-3B. Given these results, E2F-3B is missing 101 N-terminal amino acids relative to full-length E2F-3. This region includes a moderately conserved sequence of unknown function that is present only in the growth-promoting E2F family members, including E2F-1, 2 and full-length E2F-3. These observations make E2F-3B the first example of an E2F gene giving rise to two different protein species and also suggest that E2F-3 and E2F-3B may have opposing roles in cell cycle control.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Allen KE, de la Luna S, Kerkhoven RM, Bernards R and La Thangue NB. . 1997 J. Cell. Sci. 110: 2819–2831.

  • Arnaud E, Touriol C, Boutonnet C, Gensac MC, Vagner S, Prats H and Prats AC. . 1999 Mol. Cell. Biol. 19: 505–514.

  • Bandara LR, Buck VM, Zamanian M, Johnston LH and La Thangue NB. . 1993 EMBO J. 12: 4317–4324.

  • Beijersbergen RL, Kerkhoven RM, Zhu L, Carlee L, Voorhoeve PM and Bernards R. . 1994 Genes Dev. 8: 2680–2690.

  • Boyd L and Thummel CS. . 1993 Proc. Natl. Acad. Sci. U S A. 90: 9164–9167.

  • Buck V, Allen KE, Sorensen T, Bybee A, Hijmans EM, Voorhoeve PM, Bernards R and La Thangue NB. . 1995 Oncogene 11: 31–38.

  • Bugler B, Amalric F and Prats H. . 1991 Mol. Cell. Biol. 11: 573–577.

  • Cartwright P, Muller H, Wagener C, Holm K and Helin K. . 1998 Oncogene 17: 611–623.

  • Chellappan SP, Hiebert S, Mudryj M, Horowitz JM and Nevins JR. . 1991 Cell 65: 1053–1061.

  • Coligan J, Dunn B, Ploegh H, Speicher D, Wingfield P and Chanda V. . Current protocols in protein science. John Wiley and Sons. Inc.

  • Couderc B, Prats H, Bayard F and Amalric F. . 1991 Cell. Regul. 2: 709–718.

  • Cress WD, Johnson DG and Nevins JR. . 1993 Mol. Cell. Biol. 13: 6314–6325.

  • Cress WD and Nevins JR. . 1994 J. Virol. 68: 4213–4219.

  • Cress WD and Nevins JR. . 1996 Mol. Cell. Biol. 16: 2119–2127.

  • DeGregori J, Leone G, Miron A, Jakoi L and Nevins JR. . 1997 Proc. Natl. Acad. Sci. USA 94: 7245–7250.

  • Dong F, Cress Jr WD, Agrawal D and Pledger WJ. . 1998 J. Biol. Chem. 273: 6190–6195.

  • Dyson N. . 1998 Genes Dev. 12: 2245–2262.

  • Falvey E, Fleury-Olela F and Schibler U. . 1995 EMBO J. 14: 4307–4317.

  • Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin Jr WG, Livingston DM, Orkin SH and Greenberg ME. . 1996 Cell 85: 549–561.

  • Flores AM, Kassatly RF and Cress WD. . 1998 Oncogene 16: 1289–1298.

  • Gaubatz S, Wood JG and Livingston DM. . 1998 Proc. Natl. Acad. Sci. USA 95: 9190–9195.

  • Ginsberg D, Vairo G, Chittenden T, Xiao ZX, Xu G, Wydner KL, DeCaprio JA, Lawrence JB and Livingston DM. . 1994 Genes Dev 8: 2665–2679.

  • Hann SR. . 1994 Biochimie 76: 880–886.

  • Hann SR. . 1995 Adv. Exp. Med. Biol. 375: 107–116.

  • Hann SR, Dixit M, Sears RC and Sealy L. . 1994 Genes. Dev. 8: 2441–2452.

  • Hann SR, King MW, Bentley DL, Anderson CW and Eisenman RN. . 1988 Cell 52: 185–195.

  • Hann SR, Sloan-Brown K and Spotts GD. . 1992 Genes Dev. 6: 1229–1240.

  • Helin K and Harlow E. . 1994 J. Virol. 68: 5027–5035.

  • Helin K, Lees JA, Vidal M, Dyson N, Harlow E and Fattaey A. . 1992 Cell 70: 337–350.

  • Helin K, Wu C-L, Lees JA, Dynlacht BD, Ngwu C and Harlow E. . 1993 Genes. Dev. 7: 1850–1861.

  • Hijmans EM, Voorhoeve PM, Beijersbergen RL, van’t Veer LJ and Bernards R. . 1995 Mol. Cell. Biol. 15: 3082–3089.

  • Hsiao KM, McMahon SL and Farnham PJ. . 1994 Genes Dev 8: 1526–1537.

  • Humbert PO, Verona R, Trimarchi JM, Rogers C, Dandapani S and Lees JA. . 2000 Genes Dev. 14: 690–703.

  • Hurford Jr RK, Cobrinik D, Lee MH and Dyson N. . 1997 Genes Dev. 11: 1447–1463.

  • Ikeda MA, Jakoi L and Nevins JR. . 1996 Proc. Natl. Acad. Sci. USA 93: 3215–3220.

  • Imataka H, Olsen HS and Sonenberg N. . 1997 EMBO J. 16: 817–825.

  • Itoh A, Levinson SF, Morita T, Kourembanas S, Brody JS and Mitsialis SA. . 1995 Cell. Mol. Biol. Res. 41: 147–154.

  • Ivey-Hoyle M, Conroy R, Huber HE, Goodhart PJ, Oliff A and Heimbrook DC. . 1993 Mol. Cell. Biol. 13: 7802–7812.

  • Johnson DG, Ohtani K and Nevins JR. . 1994 Genes Dev. 8: 1514–1525.

  • Johnson DG and Schneider-Broussard R. . 1998 Front. Biosci. 3: 447–448.

  • Johnson DG, Schwarz JK, Cress WD and Nevins JR. . 1993 Nature 365: 349–352.

  • Kaelin Jr WG, Krek W, Sellers WR, DeCaprio JA, Ajchenbaum F, Fuchs CS, Chittenden T, Li Y, Farnham PJ, Blanar MA, Livingston DM and Flemington EK. . 1992 Cell 70: 351–364.

  • Karlseder J, Rotheneder H and Wintersberger E. . 1996 Mol. Cell. Biol. 16: 1659–1667.

  • Kitagawa M, Higashi H, Suzuki-Takahashi I, Segawa K, Hanks SK, Taya Y, Nishimura S and Okuyama A. . 1995 Oncogene 10: 229–236.

  • Krek W, Ewen ME, Shirodkar S, Arany Z, Kaelin Jr WG and Livingston DM. . 1994 Cell 78: 161–172.

  • Krek W, Xu G and Livingston DM. . 1995 Cell 83: 1149–1158.

  • Lees JA, Saito M, Vidal M, Valentine M, Look T, Harlow E, Dyson N and Helin K. . 1993 Mol. Cell. Biol. 13: 7813–7825.

  • Leone G, DeGregori J, Yan Z, Jakoi L, Ishida S, Williams RS and Nevins JR. . 1998 Genes. Dev. 12: 2120–2130.

  • Lin SY, Black AR, Kostic D, Pajovic S, Hoover CN and Azizkhan JC. . 1996 Mol. Cell. Biol. 16: 1668–1675.

  • Lindeman GJ, Dagnino L, Gaubatz S, Xu Y, Bronson RT, Warren HB and Livingston DM. . 1998 Genes Dev. 12: 1092–1098.

  • Lindeman GJ, Gaubatz S, Livingston DM and Ginsberg D. . 1997 Proc. Natl. Acad. Sci. USA 94: 5095–5100.

  • Lukas J, Petersen BO, Holm K, Bartek J and Helin K. . 1996 Mol. Cell. Biol. 16: 1047–1057.

  • Madigan SJ, Edeen P, Esnayra J and McKeown M. . 1996 Mol. Cell. Biol. 16: 4222–4230.

  • Magae J, Wu CL, Illenye S, Harlow E and Heintz NH. . 1996 J. Cell. Sci. 109: 1717–1726.

  • Mann DJ and Jones NC. . 1996 Curr Biol. 6: 474–483.

  • Moberg K, Starz MA and Lees JA. . 1996 Mol. Cell. Biol. 16: 1436–1449.

  • Morkel M, Wenkel J, Bannister AJ, Kouzarides T and Hagemeier C. . 1997 Nature 390: 567–568.

  • Muller H, Moroni MC, Vigo E, Petersen BO, Bartek J and Helin K. . 1997 Mol. Cell. Biol. 17: 5508–5520.

  • Neuman E, Flemington EK, Sellers WR and Kaelin Jr WG. . 1994 Mol. Cell. Biol. 14: 6607–6615.

  • Nevins JR. . 1998 Cell. Growth Differ 9: 585–593.

  • Peabody DS. . 1989 J. Biol. Chem. 264: 5031–5035.

  • Persengiev SP, Kondova II and Kilpatrick DL. . 1999 Mol. Cell. Biol. 19: 6048–6056.

  • Pierce AM, Schneider-Broussard R, Philhower JL and Johnson DG. . 1998 Mol. Carcinog 22: 190–198.

  • Riechmann JL, Ito T and Meyerowitz EM. . 1999 Mol. Cell. Biol. 19: 8505–8512.

  • Rogers KT, Higgins PD, Milla MM, Phillips RS and Horowitz JM. . 1996 Proc. Natl. Acad. Sci. USA 93: 7594–7599.

  • Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A and Weinberg RA. . 1995 Proc. Natl. Acad. Sci. USA 92: 2403–2407.

  • Sears R, Ohtani K and Nevins JR. . 1997 Mol. Cell. Biol. 17: 5227–5235.

  • Shan B, Zhu X, Chen PL, Durfee T, Yang Y, Sharp D and Lee WH. . 1992 Mol. Cell. Biol. 12: 5620–5631.

  • Shin EK, Tevosian SG and Yee AS. . 1996 J. Biol. Chem. 271: 12261–12268.

  • Spotts GD, Patel SV, Xiao Q and Hann SR. . 1997 Mol. Cell. Biol 17: 1459–1468.

  • Tao Y, Kassatly RF, Cress WD and Horowitz JM. . 1997 Mol. Cell. Biol 17: 6994–7007.

  • Trimarchi JM, Fairchild B, Verona R, Moberg K, Andon N and Lees JA. . 1998 Proc. Natl. Acad. Sci. USA 95: 2850–2855.

  • Verona R, Moberg K, Estes S, Starz M, Vernon JP and Lees JA. . 1997 Mol. Cell. Biol. 17: 7268–7282.

  • Wu CL, Zukerberg LR, Ngwu C, Harlow E and Lees JA. . 1995 Mol. Cell. Biol. 15: 2536–2546.

  • Xiao JH, Davidson I, Matthes H, Garnier JM and Chambon P. . 1991 Cell 65: 551–568.

  • Xiao Q, Claassen G, Shi J, Adachi S, Sedivy J and Hann SR. . 1998 Genes Dev 12: 3803–3808.

  • Xu M, Sheppard KA, Peng CY, Yee AS and Piwnica-Worms H. . 1994 Mol. Cell. Biol. 14: 8420–8431.

  • Yamasaki L, Jacks T, Bronson R, Goilot E, Harlow E and Dyson NJ. . 1996 Cell 85: 537–548.

  • Zhang Y and Chellappan SP. . 1995 Oncogene 10: 2085–2093.

Download references

Acknowledgements

We thank Kip Wharton, Gene Ness, and Rhonda Croxton for critical comments on the manuscript. We thank Nancy Olashaw, Tere Muñoz-Antonia, Ed Seto and Ken Wright for helpful discussions. The Moffitt Flow Cytometry and Molecular Biology Core Facilities performed flow cytometry and DNA sequencing, respectively. This work was supported by NCI Grant #CA78214 to WDC, by a graduate fellowship to Y He from the American Heart Association, Florida/Puerto Rico Affiliate and by the H. Lee Moffitt Cancer Center and Research Institute. MJ Thomas is a Fellow of the Leukemia and Lymphoma Society.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Program in Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, College of Medicine, Tampa, 33612, Florida, FL, USA

    Yiwen He, Michael K Armanious & W Douglas Cress

  2. Department of Medical Microbiology, University of South Florida, College of Medicine, Tampa, 33612, Florida, FL, USA

    Matthew J Thomas

Authors
  1. Yiwen He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael K Armanious
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew J Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W Douglas Cress
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, Y., Armanious, M., Thomas, M. et al. Identification of E2F-3B, an alternative form of E2F-3 lacking a conserved N-terminal region. Oncogene 19, 3422–3433 (2000). https://doi.org/10.1038/sj.onc.1203682

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203682

Keywords

This article is cited by

Search

Advanced search

Quick links