Abstract
Rb2/p130, a member of the Retinoblastoma family of growth and tumour suppressor genes, is extensively implicated in the control of cell cycle and differentiation. The minimal promoter region of Rb2/p130 in T98G human glioblastoma cells was identified and its analysis revealed the presence of a KER1 palindromic sequence able to bind the transcription factor AP-2, a regulatory protein that plays a crucial role in ectodermal differentiation. This KER1 site interacted in vitro with AP-2, and AP-2 overexpression increased Rb2/p130 transcription and translation. We also found that rat PC12 pheochromocytoma cells, when induced to differentiate by NGF, displayed an increase of AP-2 protein levels and of Rb2/p130 transcription and protein levels. AP-2-transfected PC12 cells displayed enhanced transcription and translation of Rb2/p130 and of the cdk inhibitor p21WAF1/CIP1, a gene known to be under the control of AP-2, but unable by itself to elicit PC12 differentiation. Overexpression of either AP-2 or Rb2/p130 elicited per se cell differentiation in the absence of NGF, while coexpression of AP-2B, a negative regulator of AP-2 transcriptional activity, inhibited only AP-2-induced differentiation. Altogether, these results indicate that Rb2/p130 is a critical effector of AP-2 in sustaining ectodermal differentiation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Abbreviations
- CAT:
-
chloramphenicol acetyltransferase
- EMSA:
-
electrophoretic mobility shift assay
- SDS–PAGE:
-
polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate
- S.D.:
-
Standard Deviation.
References
Baldi A, Boccia V, Claudio PP, De Luca A, Giordano A . 1996 Proc. Natl. Acad. Sci. USA 93: 4629–4632
Baldi A, De Luca A, Claudio PP, Baldi F, Giordano GG, Tommasino M, Paggi MG, Giordano A . 1995 J. Cell Biochem. 59: 402–408
Baldi A, Esposito V, De Luca A, Fu Y, Meoli I, Giordano GG, Caputi M, Baldi F, Giordano A . 1997 Clin. Cancer Res. 3: 1691–1697
Batsche E, Muchardt C, Behrens J, Hurst HC, Cremisi C . 1998 Mol. Cell Biol. 18: 3647–3658
Bennett GS, DiLullo C . 1985 Dev. Biol. 107: 94–106
Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP . 1995 Proc. Natl. Acad. Sci. USA 92: 7297–7301
Buettner R, Kannan P, Imhof A, Bauer R, Yim SO, Glockshuber R, Van Dyke MW, Tainsky MA . 1993 Mol. Cell. Biol. 13: 4174–4185
Claudio PP, Howard CM, Baldi A, De Luca A, Fu Y, Condorelli G, Sun Y, Colburn N, Calabretta B, Giordano A . 1994 Cancer Res. 54: 5556–5560
Di Fiore B, Palena A, Felsani A, Palitti F, Caruso M, Lavia P . 1999 Nucleic Acids Res. 27: 2852–2859
el-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y. et al . 1994 Cancer Res. 54: 1169–1174
Erhardt JA, Pittman RN . 1998 Oncogene 16: 443–451
Fajas L, Le Cam L, Polanowska J, Fabbrizio E, Servant N, Philips A, Carnac G, Sardet C . 2000 FEBS Lett. 471: 29–33
Fuchs E, Byrne C . 1994 Curr. Opin. Genet. Dev. 4: 725–736
Garriga J, Limón A, Mayol X, Rane SG, Albrecht JH, Reddy EP, Andrés V, Graña X . 1998 Biochem. J. 333: 645–654
Gaubatz S, Imhof A, Dosch R, Werner O, Mitchell P, Buettner R, Eilers M . 1995 EMBO J. 14: 1508–1519
Gervasi F, D'Agnano I, Vossio S, Zupi G, Sacchi A, Lombardi D . 1996 Cell Growth Differ. 7: 1689–1695
Greene LA, Tischler AS . 1976 Proc. Natl. Acad. Sci. USA 73: 2424–2428
Halevy O, Novitch BG, Spicer DB, Skapek SX, Rhee J, Hannon GJ, Beach D, Lassar AB . 1995 Science 267: 1018–1021
Hurford Jr RK, Cobrinik D, Lee MH, Dyson N . 1997 Genes Dev. 11: 1447–1463
Kalman D, Whittaker K, Bishop JM, O'Lague PH . 1993 Mol. Biol. Cell 4: 353–361
Kiess M, Gill RM, Hamel PA . 1995 Cell Growth Differ. 6: 1287–1298
Leask A, Byrne C, Fuchs E . 1991 Proc. Natl. Acad. Sci. USA 88: 7948–7952
Leask A, Rosenberg M, Vassar R, Fuchs E . 1990 Genes Dev. 4: 1985–1998
Luscher B, Mitchell PJ, Williams T, Tjian R . 1989 Genes Dev. 3: 1507–1517
Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T . 1995 Genes Dev. 9: 935–944
Martelli F, Cenciarelli C, Santarelli G, Polikar B, Felsani A, Caruso M . 1994 Oncogene 9: 3579–3590
Mitchell PJ, Timmons PM, Hebert JM, Rigby PW, Tjian R . 1991 Genes Dev. 5: 105–119
Mitchell PJ, Wang C, Tjian R . 1987 Cell 50: 847–861
Mulligan G, Jacks T . 1998 Trends Genet. 14: 223–229
Nevins JR . 1998 Cell Growth Differ. 9: 585–593
Olopade OI, Jenkins RB, Ransom DT, Malik K, Pomykala H, Nobori T, Cowan JM, Rowley JD, Diaz MO . 1992 Cancer Res. 52: 2523–2529
Paggi MG, Baldi A, Bonetto F, Giordano A . 1996 J. Cell. Biochem. 62: 418–430
Paramio JM, LaÃn S, Segrelles C, Lane EB, Jorcano JL . 1998 Oncogene 17: 949–957
Persengiev SP, Kondova II, Kilpatrick DL . 1999 Mol. Cell. Biol. 19: 6048–6056
Pertile P, Baldi A, De Luca A, Bagella L, Virgilio L, Pisano MM, Giordano A . 1995 Cell Growth Differ. 6: 1659–1664
Philipp J, Mitchell PJ, Malipiero U, Fontana A . 1994 Dev. Biol. 165: 602–614
Puri PL, Cimino L, Fulco M, Zimmerman C, La Thangue NB, Giordano A, Graessmann A, Levrero M . 1998 Cancer Res. 58: 1325–1331
Raschellà G, Tanno B, Bonetto F, Amendola R, Battista T, De Luca A, Giordano A, Paggi MG . 1997 J. Cell. Biochem. 67: 297–303
Raschellà G, Tanno B, Bonetto F, Negroni A, Claudio PP, Baldi A, Amendola R, Calabretta B, Giordano A, Paggi MG . 1998 Cell Death Differ. 5: 401–407
Richon VM, Lyle RE, McGehee Jr RE . 1997 J. Biol. Chem. 272: 10117–10124
Riley DJ, Lee EYHP, Lee W-H . 1994 Annu. Rev. Cell Biol. 10: 1–29
Schorle H, Meier P, Buchert M, Jaenisch R, Mitchell PJ . 1996 Nature 381: 235–238
Sidle A, Palaty C, Dirks P, Wiggan O, Kiess M, Gill RM, Wong AK, Hamel PA . 1996 Crit. Rev. Biochem. Mol. Biol. 31: 237–271
Somasundaram K, Jayaraman G, Williams T, Moran E, Frisch S, Thimmapaya B . 1996 Proc. Natl. Acad. Sci. USA 93: 3088–3093
Steinman RA, Hoffman B, Iro A, Guillouf C, Liebermann DA, el Houseini ME . 1994 Oncogene 9: 3389–3396
Van Grunsven LA, Billon N, Savatier P, Thomas A, Urdiales JL, Rudkin BB . 1996 Oncogene 12: 1347–1356
Williams T, Admon A, Luscher B, Tjian R . 1988 Genes Dev. 2: 1557–1569
Williams T, Tjian R . 1991 Genes Dev. 5: 670–682
Winning RS, Shea LJ, Marcus SJ, Sargent TD . 1991 Nucleic. Acids. Res. 19: 3709–3714
Wu F, Lee AS . 1998 Nucleic. Acids. Res. 26: 4837–4845
Yan GZ, Ziff EB . 1997 J. Neurosci. 17: 6122–6132
Zeng YX, Somasundaram K, el-Deiry WS . 1997 Nature Genetics 15: 78–82
Zhang J, Hagopian-Donaldson S, Serbedzija G, Elsemore J, Plehn-Dujowich D, McMahon AP, Flavell RA, Williams T . 1996 Nature 381: 238–241
Acknowledgements
The Authors thank Drs PG Natali, O Segatto, R Tecce (deceased), G Piaggio, A De Luca, M Cippitelli, P Russo, E Palescandolo (Istituto Regina Elena, Rome, Italy) and C Vesco (CNR, Rome) for useful suggestions and criticism, Dr MA Tainsky (Wayne State University, Detroit, MI, USA) for the gift of AP-2 and AP-2B expression plasmids and Dr D Mercanti (CNR, Istituto di Neurobiologia, Rome, Italy) for kindly providing NGF. This work was supported in part by AIRC grants to MG Paggi and A Felsani, by Ministero della Sanità grants to MG Paggi, A Felsani and D Lombardi and by NIH grants RO1 CA 60999-01A1 and PO1 NS 36466 and in part by the Sbarro Institute for Molecular Medicine to A Giordano. F Bonetto and A Baldi were supported by a FIRC post-doctoral fellowship. F Bucci was supported by a CNR fellowship.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Paggi, M., Bonetto, F., Severino, A. et al. The retinoblastoma-related Rb2/p130 gene is an effector downstream of AP-2 during neural differentiation. Oncogene 20, 2570–2578 (2001). https://doi.org/10.1038/sj.onc.1204356
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204356
Keywords
This article is cited by
-
Hepatitis C virus core protein modulates pRb2/p130 expression in human hepatocellular carcinoma cell lines through promoter methylation
Journal of Experimental & Clinical Cancer Research (2015)
-
Identification of genes differentially expressed as result of adenovirus type 5- and adenovirus type 12-transformation
BMC Genomics (2009)
-
AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells
Oncogene (2006)
-
Expression of Rb2/p130 protein correlates with the degree of malignancy in gliomas
Brain Tumor Pathology (2004)
-
Interplay between the antimetastatic nm23 and the Retinoblastoma-related Rb2/p130 genes in promoting neuronal differentiation of PC12 cells
Cell Death & Differentiation (2001)