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:

Site-specific and temporally-regulated retinoblastoma protein dephosphorylation by protein phosphatase type 1

Abstract

pRb is dephosphorylated at mitotic exit by the type 1 serine/threonine protein phosphatases (PP1). Here we demonstrate for the first time that mitotic pRb dephosphorylation is a sequential, temporally-regulated event. We also provide evidence that the three mammalian isoforms of PP1, α, γ-1, and δ, differ in their respective preferences for site-specific pRb dephosphorylation and that the mitotic and G1 PP1-isoform counterparts exhibit differential activities towards mitotic pRb. Finally, the physiological relevance of the striking contrast between the patterns of Thr821 and Thr826 dephosphorylation, sites known to be important for disrupting binding of LXCXE-containing proteins to pRb, is addressed.

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

Similar content being viewed by others

References

  • Alberts AS, Thorburn AM, Shenolikar S, Mumby MC, Feramisco JR . 1993 Proc. Natl. Acad. Sci. USA 90: 388–392

  • Allen PB, Kwon Y-G, Nairn AC, Greengard P . 1998 J. Biol. Chem. 273: 4089–4095

  • Bartek J, Barkkova J, Lukas J . 1996 Curr. Opin. Cell. Biol. 8: 805–814

  • Boylan JF, Sharp DM, Leffet L, Bowers A, Pan W . 1999 Exp. Cell. Res. 248: 110–114

  • Buchkovich KL, Duffy A, Harlow E . 1989 Cell 58: 1097–1105

  • Chen P-L, Scully P, Shew Y-Y, Wang JYJ, Lee W-H . 1989 Cell 58: 1193–1198

  • Chew YP, Ellis M, Wilkie S, Mittnacht S . 1998 Oncogene 17: 2177–2186

  • Connell-Crowley L, Harper JW, Goodrich DW . 1997 Mol. Biol. Cell 8: 287–301

  • DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang C-M, Livingston DM . 1989 Cell 58: 1085–1095

  • Dohadwala M, da Cruz e Silva DF, Hall FL, Williams RT, Carbonaro-Hall DA, Nairn AC, Greengard P, Berndt N . 1994 Proc. Natl. Acad. Sci. USA 91: 6408–6412

  • Durfee T, Becherer K, Chen P-L, Yeh S-H, Yang Y, Kilburn AE, Lee W-H, Elledge SJ . 1993 Genes Dev. 7: 555–569

  • Harbour JW, Luo RX, DeSanti A, Postigo AA, Dean DC . 1999 Cell 98: 859–869

  • Harlow E, Crawford LV, Pim DC, Williamson NM . 1981 J. Virol. 39: 861–869

  • Herwig S, Strauss M . 1997 Eur. J. Biochem. 246: 581–601

  • Kitagawa M, Higashi H, Jung H-K, Suzuki-Takahashi I, Ideka M, Tamai K, Kato J-Y, Segawa K, Yoshida E, Nishimura S, Taya Y . 1996 EMBO J. 15: 7060–7069

  • Knudsen ES, Wang JYJ . 1996 J. Biol. Chem. 271: 8313–8320

  • Kwon Y-G, Lee SY, Choi Y, Greengard P, Nairn AC . 1997 Proc. Natl. Acad. Sci. USA 94: 2168–2173

  • Liu CWY, Wang R-H, Dohadwala M, Schonthal AH, Villa-Moruzzi E, Berndt N . 1999 J. Biol. Chem. 274: 29470–29475

  • Ludlow JW, Glendening CL, Livingston DM, DeCaprio JA . 1993 Mol. Cell. Biol. 13: 367–372

  • Ludlow JW, Shon J, Pipas JM, Livingston DM, DeCaprio JA . 1990 Cell 60: 387–396

  • Lundberg A, Weinberg RA . 1998 Mol. Cell. Biol. 18: 753–761

  • Lussow AR, Barrios C, Embden JV, Zee RV, Verdini AS, Pesi A, Louis JA, Lambert P-H, Giudice GD . 1991 Eur. J. Immunol. 21: 2297–2302

  • Mihara K, Cao X-R, Yen A, Chandler S, Driscoll B, Murphree AL, T'Ang A, Fung Y-KT . 1989 Science 246: 1300–1303

  • Mittnacht S, Lees JA, Desai D, Harlow E, Morgan DO, Weinberg RA . 1994 EMBO J. 13: 118–127

  • Nakaya N, Lowe SW, Taya Y, Chenchik A, Enikolopov G . 2000 Oncogene 19: 6369–6375

  • Nelson DA, Ludlow JW . 1997 Oncogene 14: 2407–2415

  • Nelson DA, Krucher NA, Ludlow JW . 1997 J. Biol. Chem. 272: 4528–4535

  • Pardee AB . 1974 Proc. Natl. Acad. Sci. USA 71: 1286–1290

  • Puntoni F, Villa-Moruzzi E . 1997 Mol. Cell. Biochem. 171: 115–120

  • Tamrakar S, Mittnacht S, Ludlow JW . 1999 Oncogene 18: 7803–7809

  • Tamrakar S, Ludlow JW . 2000 J. Biol. Chem. 275: 27784–27789

  • Todaro GJ, Green H, Swift MR . 1966 Science 153: 1252–1254

  • Tognarini M, Villa-Moruzzi E . 1998 Protein Phosphatase Protocols. Ludlow JW. ed Humana Press: New Jersey pp. 169–183

  • Towbin H, Staehelin T, Gordon J . 1979 Proc. Natl. Acad. Sci. USA 76: 4350–4354

  • Umstott-Hall K, Collins SP, Gamm DM, Massa E, DePaoli-Roach AA, Uhler MD . 1999 J. Biol. Chem. 274: 3485–3495

  • Wera S, Hemmings BA . 1995 Biochem. J. 311: 17–29

  • Yan Y, Mumby MC . 1999 J. Biol. Chem. 274: 31917–31924

  • Zarkowska T, Mittnacht S . 1997 J. Biol. Chem. 272: 12738–12746

Download references

Acknowledgements

This work was supported by Research Project Grant # 98-108 from the American Cancer Society, The Sally Edelman and Harry Gardner Cancer Research Foundation (awarded to JW Ludlow), and Cancer Center Core Grant CA11198.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John W Ludlow.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rubin, E., Mittnacht, S., Villa-Moruzzi, E. et al. Site-specific and temporally-regulated retinoblastoma protein dephosphorylation by protein phosphatase type 1. Oncogene 20, 3776–3785 (2001). https://doi.org/10.1038/sj.onc.1204518

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204518

Keywords

This article is cited by

Search

Quick links