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:

Amphiphysin IIb-1, a novel splicing variant of amphiphysin II, regulates p73β function through protein-protein interactions

Abstract

p73 is a nuclear protein that is similar in structure and function to p53. Notably, the C-terminal region of p73 has a regulatory function, through interactions with a positive or negative regulator. In this study, we use the yeast two-hybrid technique to identify a novel p73β binding protein, designated amphiphysin IIb-1. Amphiphysin IIb-1 is one of the splicing variants of amphiphysin II, and has a shorter protein product than amphiphysin IIb, which has been previously reported. We confirmed that amphiphysin IIb-1 binds full-length p73β, both in vitro and in vivo. This association is mediated via the SH3 domain of amphiphysin IIb-1 and C-terminal amino acids 321–376 of p73β. Double immunofluorescence patterns revealed that p73β is relocalized to the cytoplasm in the presence of amphiphysin IIb-1. Overexpression of amphiphysin IIb-1 was found to significantly inhibit the transcriptional activity of p73β in a dose-dependent manner. In addition, the cell death function of p73β was inhibited by amphiphysin IIb-1. These findings offer a new insight into the regulation mechanism of p73β, and suggest that amphiphysin IIb-1 modulates p73β function by direct binding.

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

Access options

Buy this article

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
Figure 8

Similar content being viewed by others

References

  • Agami R, Blandino G, Oren M, Shaul Y . 1999 Nature 399: 809–813

  • Bauer F, Urdaci M, Aigle M, Crouzet M . 1993 Mol. Cell Biol. 13: 5070–5084

  • Butler MH, David C, Ochoa G-C, Freyberg Z, Daniell L, Grabs D, Cremona O, De Camilli P . 1997 J. Cell. Biol. 137: 1355–1367

  • Darzynkiewicz Z, Bruno S, Del Bino G, Gorczyca W, Hotz MA, Lassota P, Traganos F . 1992 Cytometry 13: 795–808

  • David C, McPherson PS, Mundigl O, De Camilli P . 1996 Proc. Natl. Acad. Sci. USA. 93: 331–335

  • Davison TS, Vagner C, Kaghad M, Ayed Caput D, Arrowsmith CH . 1999 J. Biol. Chem. 274: 18709–18714

  • De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annicchiarico-Petruzzelli M, Levrero M, Melino G . 1998 J. Exp. Med. 188: 1763–1768

  • Di Como CJ, Gaiddon C, Prives C . 1999 Mol. Cell Biol. 19: 1438–1449

  • Dobbelstein M, Wienzek S, Konig C, Roth J . 1999 Oncogene 18: 2101–2106

  • Elliott K, Sakamuro D, Basu A, Du W, Wunner W, Staller P, Gaubatz S, Zhang H, Prochownik E, Eilers M, Prendergast GC . 1999 Oncogene 18: 3564–3573

  • Estojak J, Brent R, Golemis EA . 1995 Mol. Cell Biol. 15: 5820–5829

  • Field S, Song OK . 1989 Nature 340: 245–246

  • Ge K, Prendergast GC . 2000 Genomics 67: 210–220

  • Gong J, Costanzo A, Yang H-Q, Melino G, Kaelin Jr WG, Levrero M, Wang JY . 1999 Nature 399: 806–809

  • Gyuris J, Golemis E, Chertkov H, Brent R . 1993 Cell 75: 791–803

  • Horvath A, Riezman H . 1994 Yeast 10: 1305–1310

  • Haupt Y, Maya R, Kazaz A, Oren M . 1997 Nature 387: 296–299

  • Hoffmann CS, Winston F . 1987 Gene 57: 267–272

  • Ichimiya S, Nimura Y, Kageyama H, Takada N, Sunahara M, Shishikura T, Nakamura Y, Sakiyama S, Seki N, Ohira M, Kaneko Y, McKeon F, Caput D, Nakagawara A . 1999 Oncogene 18: 1061–1066

  • Jost CA, Marin MC, Kaelin Jr WG . 1997 Nature 389: 191–194

  • Kadlec L, Prendergast AM . 1997 Proc. Natl. Acad. Sci. USA 94: 12390–12395

  • Kaghad M, bonnet H, Yang A, Yang A, Creancier L, Biscan J-C, Valent A, Minty A, Chalon P, Lelias J-M, Dumont X, Ferraa P, Caput D . 1997 Cell 90: 809–819

  • Kim I-S, Kim D-H, Han S-M, Chin M-U, Nam H-J, Cho H-P, Chio S-Y, Song B-J, Kim E-U, Bae Y-S, Moon Y-H . 2000 J. Biol. Chem. 275: 23139–23145

  • Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H . 1997 Am. J. Pathol. 150: 1–13

  • Le Douarin B, Prerrat B, vom Baur E, Chambon P, Losson R . 1995 Nucleic Acids Res. 23: 876–878

  • Li S, Ku C-Y, Farmer AA, Cong Y-S, Chen C-F, Lee W-H . 1998 J. Biol. Chem. 273: 6183–6189

  • Licitra EJ, Liu JO . 1996 Proc. Natl. Acad. Sci. USA 93: 12817–12821

  • Martin MC, Jost CA, Irwin MS, DeCaprio JA, Caput D, Kaelin Jr WG . 1998 Mol. Cell. Biol. 18: 6316–6324

  • Moll UM, Riou G, Levine AJ . 1992 Pro. Natl. Acad. Sci. USA 89: 7262–7266

  • Moll UM, Ostermeyer AG, Haladay R, Winkfield B, Frazier M, Zamberri G . 1996 Mol. Cell. Biol. 16: 1126–1137

  • Ostermeyer AG, Runko E, Winkfield B, Ahn B, Moll UM . 1996 Proc. Natl. Acad. Sci. USA 93: 15190–15194

  • Ozaki T, Naka M, Takada N, Tada M, Sakiyama S, Nakagawara A . 1999 Cancer Res. 59: 5902–5907

  • Ramjaun AR, McPherson PS . 1997 J. Neurochem. 70: 2369–2376

  • Roth J, Konig C, Wienzek S, Weigel S, Ristea S, Dobbelstein M . 1998 J. Virol. 72: 8510–8516

  • Sakamuro D, Elliott KJ, Wechsler-Reya R, Prendergast GC . 1996 Nat. Genet. 14: 69–77

  • Steegenga WT, Shvarts A, Riteco N, Bos J, Jochemsem AG . 1999 Mol. Cell. Biol. 19: 3885–3894

  • Strano S, Munarriz E, Rossi M, Cristofanelli B, Shaul Y, Castagnoli L, Levine AJ, Sacchi A, Cesareni G, Oren M, Blandino G . 2000 J. Biol. Chem. 275: 29503–29512

  • Tirode F, Malaguti C, Romero F, Attar R, Camonis J, Egly JM . 1997 J. Biol. Chem. 272: 22995–22999

  • Tsutsui K, Maeda Y, Tsutsui K, Seki S, Tokunaga A . 1997 Biochem. Biophys. Res. Commun. 236: 178–183

  • Ueda Y, Hijikata M, Takagi S, Chiba T, Shimotohno K . 1999 Oncogene 18: 4993–4998

  • Wadgaonkar R, Collins T . 1999 J. Biol. Chem. 20: 13760–13767

  • Wienzek S, Roth J, Dobbelstein M . 2000 J. Virol. 74: 193–202

  • Yuan Z-M, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, Lu H, Kharbanda S, Weichselbaum R, Kufe D . 1999 Nature 399: 814–817

  • Zeng Z, Chen L, Jost CA, Maya R, Keller D, Wang X, Kaelin WG, Oren M, Chen J, Lu H . 1999 Mol. Cell. Biol. 19: 3257–3266

Download references

Acknowledgements

We gratefully thank Dr JY Lee of Hallym University for the p21-Luc plasmid. We also thank Dr HS Lim of the Catholic Medical Center for helpful comments on the yeast two-hybrid technique. This work was supported by grant from the Korea Ministry of Health and Welfare (HMP-99-B-02-002) and the Research Grant of Chung-Ang University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyung-Hee Choi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, KC., Kim, TS., Kang, KH. et al. Amphiphysin IIb-1, a novel splicing variant of amphiphysin II, regulates p73β function through protein-protein interactions. Oncogene 20, 6689–6699 (2001). https://doi.org/10.1038/sj.onc.1204839

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204839

Keywords

This article is cited by

Search

Quick links