Skip to main content

Advertisement

Log in

Discrete phosphorylated retinoblastoma protein isoform expression in mouse tooth development

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Retinoblastoma protein (pRb) phosphorylation plays a central role in mediating cell cycle G1/S stage transition, together with E2F transcription factors. The binding of pRb to E2F is thought to be controlled by the sequential and cumulative phosphorylation of pRb at various amino acids. In addition to well characterized roles as a tumor suppressor, pRb has more recently been implicated in osteoprogenitor and other types of stem cell maintenance, proliferation and differentiation, thereby influencing the morphogenesis of developing organs. In this study, we present data characterizing the expression of pRb and three phosphorylated pRb (ppRb) isoforms—ppRbS780, ppRbS795, ppRbS807/811—in developmentally staged mouse molar and incisor teeth. Our results reveal distinct developmental expression patterns for individual ppRb isoforms in dental epithelial and dental mesenchymal cell differentiation, suggesting discrete functions in tooth development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Andreeva et al (2012) Rb1 mRNA expression in developing mouse teeth. Gene Expr Patterns. doi:10.1016/j.gep.2012.01.004

  • Boylan JF, Sharp DM et al (1999) Analysis of site-specific phosphorylation of the retinoblastoma protein during cell cycle progression. Exp Cell Res 248(1):110–114

    Article  PubMed  CAS  Google Scholar 

  • Brown VD, Phillips RA et al (1999) Cumulative effect of phosphorylation of pRB on regulation of E2F activity. Mol Cell Biol 19(5):3246–3256

    PubMed  CAS  Google Scholar 

  • Brugarolas J, Moberg K et al (1999) Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after gamma-irradiation. Proc Natl Acad Sci USA 96(3):1002–1007

    Article  PubMed  CAS  Google Scholar 

  • Clarke AR, Maandag ER et al (1992) Requirement for a functional Rb-1 gene in murine development. Nature 359(6393):328–330

    Article  PubMed  CAS  Google Scholar 

  • Cobrinik D (2005) Pocket proteins and cell cycle control. Oncogene 24(17):2796–2809

    Article  PubMed  CAS  Google Scholar 

  • DeCaprio JA, Ludlow JW et al (1989) The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell 58(6):1085–1095

    Article  PubMed  CAS  Google Scholar 

  • Dunn JM, Phillips RA et al (1988) Identification of germline and somatic mutations affecting the retinoblastoma gene. Science 241(4874):1797–1800

    Article  PubMed  CAS  Google Scholar 

  • Endicott JA, Noble ME et al (1999) Cyclin-dependent kinases: inhibition and substrate recognition. Curr Opin Struct Biol 9(6):738–744

    Article  PubMed  CAS  Google Scholar 

  • Ezhevsky SA, Ho A et al (2001) Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo. Mol Cell Biol 21(14):4773–4784

    Article  PubMed  CAS  Google Scholar 

  • Ferguson KL, McClellan KA et al (2005) A cell-autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration. EMBO J 24(24):4381–4391

    Article  PubMed  CAS  Google Scholar 

  • Gutierrez GM, Kong E et al (2008) Impaired bone development and increased mesenchymal progenitor cells in calvaria of RB1-/- mice. Proc Natl Acad Sci USA 105(47):18402–18407

    Article  PubMed  CAS  Google Scholar 

  • Harada H, Kettunen P et al (1999) Localization of putative stem cells in dental epithelium and their association with Notch and FGF signaling. J Cell Biol 147(1):105–120

    Article  PubMed  CAS  Google Scholar 

  • Hudson R, Taniguchi-Sidle A et al (1998) Alx-4, a transcriptional activator whose expression is restricted to sites of epithelial-mesenchymal interactions. Dev Dyn 213(2):159–169

    Article  PubMed  CAS  Google Scholar 

  • Jordan-Sciutto KL, Wang G et al (2000) Induction of cell-cycle regulators in simian immunodeficiency virus encephalitis. Am J Pathol 157(2):497–507

    Article  PubMed  CAS  Google Scholar 

  • Kitagawa M, Higashi H et al (1996) The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J 15(24):7060–7069

    PubMed  CAS  Google Scholar 

  • Knudsen ES, Wang JY (1996) Differential regulation of retinoblastoma protein function by specific Cdk phosphorylation sites. J Biol Chem 271(14):8313–8320

    Google Scholar 

  • Knudsen ES, Wang JY (1997) Dual mechanisms for the inhibition of E2F binding to RB by cyclin-dependent kinase-mediated RB phosphorylation. Mol Cell Biol 17(10):5771–5783

    PubMed  CAS  Google Scholar 

  • Kumamoto H, Kimi K et al (2001) Detection of cell cycle-related factors in ameloblastomas. J Oral Pathol Med 30(5):309–315

    Article  PubMed  CAS  Google Scholar 

  • Kumamoto H, Ooya K (2006) Immunohistochemical detection of retinoblastoma protein and E2 promoter-binding factor-1 in ameloblastomas. J Oral Pathol Med 35(3):183–189

    Google Scholar 

  • Lee EY, To H et al (1988) Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science 241(4862):218–221

    Article  PubMed  CAS  Google Scholar 

  • Meyerson M, Harlow E (1994) Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol 14(3):2077–2086

    PubMed  CAS  Google Scholar 

  • Mittnacht S (1998) Control of pRB phosphorylation. Curr Opin Genet Dev 8(1):21–27

    Article  PubMed  CAS  Google Scholar 

  • Mittnacht S, Weinberg RA (1991) G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell 65(3):381–393

    Article  PubMed  CAS  Google Scholar 

  • Mittnacht S, Lees JA et al (1994) Distinct sub-populations of the retinoblastoma protein show a distinct pattern of phosphorylation. EMBO J 13(1):118–127

    PubMed  CAS  Google Scholar 

  • Pande P, Mathur M et al (1998) pRb and p16 protein alterations in human oral tumorigenesis. Oral Oncol 34(5):396–403

    Article  PubMed  CAS  Google Scholar 

  • Poznic M (2009) Retinoblastoma protein: a central processing unit. J Biosci 34(2):305–312

    Article  PubMed  CAS  Google Scholar 

  • Ruiz S, Segrelles C et al (2003) Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development 130(11):2341–2353

    Article  PubMed  CAS  Google Scholar 

  • Sosa-Garcia B, Gunduz V et al (2010) A role for the retinoblastoma protein as a regulator of mouse osteoblast cell adhesion: implications for osteogenesis and osteosarcoma formation. PLoS One 5(11):e13954

    Article  PubMed  Google Scholar 

  • Takaki T, Fukasawa K et al (2005) Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro. J Biochem 137(3):381–386

    Article  PubMed  CAS  Google Scholar 

  • Thakur A, Siedlak SL et al (2008) Retinoblastoma protein phosphorylation at multiple sites is associated with neurofibrillary pathology in Alzheimer disease. Int J Clin Exp Pathol 1(2):134–146

    PubMed  CAS  Google Scholar 

  • Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81(3):323–330

    Article  PubMed  CAS  Google Scholar 

  • Wiggan O, Taniguchi-Sidle A et al (1998) Interaction of the pRB-family proteins with factors containing paired-like homeodomains. Oncogene 16(2):227–236

    Article  PubMed  CAS  Google Scholar 

  • Zarkowska T, Mittnacht S (1997) Differential phosphorylation of the retinoblastoma protein by G1/S cyclin-dependent kinases. J Biol Chem 272(19):12738–12746

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Yelick and Hinds Laboratory members for support and expert advice.

Conflict of interest

We acknowledge that there are no perceived or actual conflicts of interest to disclose, and support from ARRA funded NIH/NIDCR grant DE016962 (PCY).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pamela C. Yelick.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, W., Vazquez, B., Andreeva, V. et al. Discrete phosphorylated retinoblastoma protein isoform expression in mouse tooth development. J Mol Hist 43, 281–288 (2012). https://doi.org/10.1007/s10735-012-9404-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-012-9404-4

Keywords

Navigation