![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Research Papers
Department of Anatomy, University of Wisconsin Medical School, Madison 53706.
Abstract
Tumor suppressor proteins are believed to play a role in regulating cell cycle control during mammalian development. The E6 and E7 oncoproteins from human papillomavirus type 16 are known to affect cell growth control, at least in part, through their inactivation of cellular tumor suppressor gene products, p53 and Rb, respectively. Therefore, these viral proteins can serve as trans-dominant repressors of tumor suppressor gene function. To study the potential role of p53 and Rb in murine lens morphogenesis, we generated transgenic mice in which the expression of E6 or E7 was directed to the developing lens. Transgenic mice expressing E7 exhibited microphthalmia and cataracts, whereas transgenic mice expressing E6 exhibited cataracts without noticeable microphthalmia. Microscopic analysis of the lenses from neonatal and adult E7 transgenic mice revealed inhibition of lens fiber cell differentiation, induction of cell proliferation in spatially inappropriate regions of the lens, and apoptosis. Transgenic mice expressing a mutant E7 that is defective in Rb/p107 binding exhibited normal eyes, suggesting that the activity of Rb and/or Rb-like proteins is required for the perturbation of lens development and induction of apoptosis in E7 mice. Microscopic analysis of lenses from E6 neonatal and adult transgenic mice indicated the presence of nuclei in elongated fiber cells, suggesting that E6 inhibits lens fiber cell denucleation. Furthermore, expression of E6 inhibited the apoptotic-like DNA degradation observed in the lenses of nontransgenic 15.5-day embryos. In lenses from neonatal E6 x E7 double transgenic mice, the level of apoptosis was reduced compared with that seen in lenses from neonatal E7 mice. In adults E6 x E7 double transgenic mice, lens tumors developed, whereas in E6 or E7 only transgenic mice, tumors did not. Taken together, these results point to specific roles in lens morphogenesis for Rb and p53 and to the necessity of these tumor suppressor gene products in regulating exit from the normal cell division cycle in differentiating lens fiber cells.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. R. Latendresse, L. Muskhelishvili, A. Warbritton, and W. H. Tolleson Two Cases of Uveal Amelanotic Melanoma in Transgenic Tyr-HRAS+ Ink4a/Arf Heterozygous Mice Toxicol Pathol, October 1, 2007; 35(6): 825 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, L. Du, M. Osato, E. H. Teo, F. Qian, H. Jin, F. Zhen, J. Xu, L. Guo, H. Huang, et al. The zebrafish udu gene encodes a novel nuclear factor and is essential for primitive erythroid cell development Blood, July 1, 2007; 110(1): 99 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Zandy and S. Bassnett Proteolytic Mechanisms Underlying Mitochondrial Degradation in the Ocular Lens Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 293 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, F. Shang, Q. Liu, L. Urim, M. Zhang, and A. Taylor Ubiquitin-proteasome pathway function is required for lens cell proliferation and differentiation. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2569 - 2575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J.S. Simonson, M. J. Difilippantonio, and P. F. Lambert Two Distinct Activities Contribute to Human Papillomavirus 16 E6's Oncogenic Potential Cancer Res., September 15, 2005; 65(18): 8266 - 8273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Balsitis, F. Dick, D. Lee, L. Farrell, R. K. Hyde, A. E. Griep, N. Dyson, and P. F. Lambert Examination of the pRb-Dependent and pRb-Independent Functions of E7 In Vivo J. Virol., September 1, 2005; 79(17): 11392 - 11402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Munger, A. Baldwin, K. M. Edwards, H. Hayakawa, C. L. Nguyen, M. Owens, M. Grace, and K. Huh Mechanisms of Human Papillomavirus-Induced Oncogenesis J. Virol., November 1, 2004; 78(21): 11451 - 11460. [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Foley, H. Rosenbaum, and A. E. Griep Temporal Regulation of VEID-7-amino-4-trifluoromethylcoumarin Cleavage Activity and Caspase-6 Correlates with Organelle Loss during Lens Development J. Biol. Chem., July 30, 2004; 279(31): 32142 - 32150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Granja, M. L. Nogal, C. Hurtado, J. Salas, M. L. Salas, A. L. Carrascosa, and Y. Revilla Modulation of p53 Cellular Function and Cell Death by African Swine Fever Virus J. Virol., July 1, 2004; 78(13): 7165 - 7174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Psyrri, R. A. DeFilippis, A. P. B. Edwards, K. E. Yates, L. Manuelidis, and D. DiMaio Role of the Retinoblastoma Pathway in Senescence Triggered by Repression of the Human Papillomavirus E7 Protein in Cervical Carcinoma Cells Cancer Res., May 1, 2004; 64(9): 3079 - 3086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Horner, R. A. DeFilippis, L. Manuelidis, and D. DiMaio Repression of the Human Papillomavirus E6 Gene Initiates p53-Dependent, Telomerase-Independent Senescence and Apoptosis in HeLa Cervical Carcinoma Cells J. Virol., April 15, 2004; 78(8): 4063 - 4073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, F. Shang, Q. Liu, L. Urim, J. West-Mays, and A. Taylor Differential Regulation of Components of the Ubiquitin-Proteasome Pathway during Lens Cell Differentiation Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1194 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Knight and E. S. Robertson Epstein-Barr Virus Nuclear Antigen 3C Regulates Cyclin A/p27 Complexes and Enhances Cyclin A-Dependent Kinase Activity J. Virol., February 15, 2004; 78(4): 1981 - 1991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Nguyen, M. L. Nguyen, G. Caruana, A. Bernstein, P. F. Lambert, and A. E. Griep Requirement of PDZ-Containing Proteins for Cell Cycle Regulation and Differentiation in the Mouse Lens Epithelium Mol. Cell. Biol., December 15, 2003; 23(24): 8970 - 8981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Riley, S. Duensing, T. Brake, K. Munger, P. F. Lambert, and J. M. Arbeit Dissection of Human Papillomavirus E6 and E7 Function in Transgenic Mouse Models of Cervical Carcinogenesis Cancer Res., August 15, 2003; 63(16): 4862 - 4871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cid-Arregui, V. Juarez, and H. z. Hausen A Synthetic E7 Gene of Human Papillomavirus Type 16 That Yields Enhanced Expression of the Protein in Mammalian Cells and Is Useful for DNA Immunization Studies J. Virol., April 15, 2003; 77(8): 4928 - 4937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Kalejta, J. T. Bechtel, and T. Shenk Human Cytomegalovirus pp71 Stimulates Cell Cycle Progression by Inducing the Proteasome-Dependent Degradation of the Retinoblastoma Family of Tumor Suppressors Mol. Cell. Biol., March 15, 2003; 23(6): 1885 - 1895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. MacPherson, J. Sage, D. Crowley, A. Trumpp, R. T. Bronson, and T. Jacks Conditional Mutation of Rb Causes Cell Cycle Defects without Apoptosis in the Central Nervous System Mol. Cell. Biol., February 1, 2003; 23(3): 1044 - 1053. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Y. Tsai, D. MacPherson, D. A. Rubinson, A. Yu. Nikitin, R. Bronson, K. L. Mercer, D. Crowley, and T. Jacks ARF mutation accelerates pituitary tumor development in Rb+/- mice PNAS, December 24, 2002; 99(26): 16865 - 16870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. DeFilippis, E. C. Goodwin, L. Wu, and D. DiMaio Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells J. Virol., December 20, 2002; 77(2): 1551 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Decary, J. T. Decesse, V. Ogryzko, J. C. Reed, I. Naguibneva, A. Harel-Bellan, and C. E. Cremisi The Retinoblastoma Protein Binds the Promoter of the Survival Gene bcl-2 and Regulates Its Transcription in Epithelial Cells through Transcription Factor AP-2 Mol. Cell. Biol., November 15, 2002; 22(22): 7877 - 7888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Chauhan, W. Zhang, K. Cveklova, M. Kantorow, and A. Cvekl Identification of Differentially Expressed Genes in Mouse Pax6 Heterozygous Lenses Invest. Ophthalmol. Vis. Sci., June 1, 2002; 43(6): 1884 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Hyde and A. E. Griep Unique Roles for E2F1 in the Mouse Lens in the Absence of Functional pRB Proteins Invest. Ophthalmol. Vis. Sci., May 1, 2002; 43(5): 1509 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. I. Saavedra, L. Wu, A. de Bruin, C. Timmers, T. J. Rosol, M. Weinstein, M. L. Robinson, and G. Leone Specificity of E2F1, E2F2, and E2F3 in Mediating Phenotypes Induced by Loss of Rb Cell Growth Differ., May 1, 2002; 13(5): 215 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Gjoerup, D. Zaveri, and T. M. Roberts Induction of p53-Independent Apoptosis by Simian Virus 40 Small t Antigen J. Virol., October 1, 2001; 75(19): 9142 - 9155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lu, G. Magrane, C. Yin, D. N. Louis, J. Gray, and T. Van Dyke Selective Inactivation of p53 Facilitates Mouse Epithelial Tumor Progression without Chromosomal Instability Mol. Cell. Biol., September 1, 2001; 21(17): 6017 - 6030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Divan, J. Lawry, I. R. Dunsmore, M. A. Parsons, and J. A. Royds p53 and p21waf-1 Expression Correlates with Apoptosis or Cell Survival in Poorly Differentiated, but not Well-Differentiated, Retinoblastomas Cancer Res., April 1, 2001; 61(7): 3157 - 3163. [Abstract] [Full Text]
|
|
|
|
|
|
A. Hengstermann, L. K. Linares, A. Ciechanover, N. J. Whitaker, and M. Scheffner Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells PNAS, January 23, 2001; (2001) 31470698. [Abstract] [Full Text]
|
|
|
|
|
|
Q. Chen, F.-C. Hung, L. Fromm, and P. A. Overbeek Induction of Cell Cycle Entry and Cell Death in Postmitotic Lens Fiber Cells by Overexpression of E2F1 or E2F2 Invest. Ophthalmol. Vis. Sci., December 1, 2000; 41(13): 4223 - 4231. [Abstract] [Full Text]
|
|
|
|
|
|
C. Nicot and R. Harrod Distinct p300-Responsive Mechanisms Promote Caspase-Dependent Apoptosis by Human T-Cell Lymphotropic Virus Type 1 Tax Protein Mol. Cell. Biol., November 15, 2000; 20(22): 8580 - 8589. [Abstract] [Full Text]
|
|
|
|
|
|
D. Escalante-Alcalde, F. Recillas-Targa, C. Valencia, J. Santa-Olalla, P. Chávez, A. Marroquín, L. Gutiérrez-X, P. Gariglio, and L. Covarrubias Expression of E6 and E7 Papillomavirus Oncogenes in the Outer Root Sheath of Hair Follicles Extends the Growth Phase and Bypasses Resting at Telogen Cell Growth Differ., October 1, 2000; 11(10): 527 - 539. [Abstract] [Full Text]
|
|
|
|
|
|
B. Mannhardt, S. A. Weinzimer, M. Wagner, M. Fiedler, P. Cohen, P. Jansen-Dürr, and W. Zwerschke Human Papillomavirus Type 16 E7 Oncoprotein Binds and Inactivates Growth-Inhibitory Insulin-Like Growth Factor Binding Protein 3 Mol. Cell. Biol., September 1, 2000; 20(17): 6483 - 6495. [Abstract] [Full Text]
|
|
|
|
|
|
F. A. Dick, E. Sailhamer, and N. J. Dyson Mutagenesis of the pRB Pocket Reveals that Cell Cycle Arrest Functions Are Separable from Binding to Viral Oncoproteins Mol. Cell. Biol., May 15, 2000; 20(10): 3715 - 3727. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. W. Lowe and A. W. Lin Apoptosis in cancer Carcinogenesis, March 1, 2000; 21(3): 485 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Webster, J. Parish, M. Pandya, P. L. Stern, A. R. Clarke, and K. Gaston The Human Papillomavirus (HPV) 16 E2 Protein Induces Apoptosis in the Absence of Other HPV Proteins and via a p53-dependent Pathway J. Biol. Chem., January 7, 2000; 275(1): 87 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shintani, H. Yotsuyanagi, K. Moriya, H. Fujie, T. Tsutsumi, Y. Kanegae, S. Kimura, I. Saito, and K. Koike Induction of apoptosis after switch-on of the hepatitis B virus X gene mediated by the Cre/loxP recombination system J. Gen. Virol., December 1, 1999; 80(12): 3257 - 3265. [Abstract] [Full Text]
|
|
|
|
|
|
K. S. Choi, Y. W. Eom, Y. Kang, M. J. Ha, H. Rhee, J.-W. Yoon, and S.-J. Kim Cdc2 and Cdk2 Kinase Activated by Transforming Growth Factor-beta 1 Trigger Apoptosis through the Phosphorylation of Retinoblastoma Protein in FaO Hepatoma Cells J. Biol. Chem., November 5, 1999; 274(45): 31775 - 31783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. d. L. Coste, A. Mignon, M. Fabre, E. Gilbert, A. Porteu, T. V. Dyke, A. Kahn, and C. Perret Paradoxical Inhibition of c-myc-induced Carcinogenesis by Bcl-2 in Transgenic Mice Cancer Res., October 1, 1999; 59(19): 5017 - 5022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Seavey, M. Holubar, L. J. Saucedo, and M. E. Perry The E7 Oncoprotein of Human Papillomavirus Type 16 Stabilizes p53 through a Mechanism Independent of p19ARF J. Virol., September 1, 1999; 73(9): 7590 - 7598. [Abstract] [Full Text]
|
|
|
|
|
|
J. McCaffrey, L. Yamasaki, N. J. Dyson, E. Harlow, and A. E. Griep Disruption of Retinoblastoma Protein Family Function by Human Papillomavirus Type 16 E7 Oncoprotein Inhibits Lens Development in Part through E2F-1 Mol. Cell. Biol., September 1, 1999; 19(9): 6458 - 6468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sabbatini and F. McCormick Phosphoinositide 3-OH Kinase (PI3K) and PKB/Akt Delay the Onset of p53-mediated, Transcriptionally Dependent Apoptosis J. Biol. Chem., August 20, 1999; 274(34): 24263 - 24269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zimmermann, R. Degenkolbe, H.-U. Bernard, and M. J. O'Connor The Human Papillomavirus Type 16 E6 Oncoprotein Can Down-Regulate p53 Activity by Targeting the Transcriptional Coactivator CBP/p300 J. Virol., August 1, 1999; 73(8): 6209 - 6219. [Abstract] [Full Text]
|
|
|
|
|
|
M.-J. Liao, C. Yin, C. Barlow, A. Wynshaw-Boris, and T. van Dyke Atm Is Dispensable for p53 Apoptosis and Tumor Suppression Triggered by Cell Cycle Dysfunction Mol. Cell. Biol., April 1, 1999; 19(4): 3095 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Bond, M. F. Haughton, J. M. Rowson, P. J. Smith, V. Gire, D. Wynford-Thomas, and F. S. Wyllie Control of Replicative Life Span in Human Cells: Barriers to Clonal Expansion Intermediate Between M1 Senescence and M2 Crisis Mol. Cell. Biol., April 1, 1999; 19(4): 3103 - 3114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Brown and B. G. Wouters Apoptosis, p53, and Tumor Cell Sensitivity to Anticancer Agents Cancer Res., April 1, 1999; 59(7): 1391 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V Gottifredi, A Peschiaroli, G. Fimia, and R Maione p53-independent apoptosis induced by muscle differentiation stimuli in polyomavirus large T-expressing myoblasts J. Cell Sci., January 7, 1999; 112(14): 2397 - 2407. [Abstract] [PDF]
|
|
|
|
 |
|
 C. J. Sherr Tumor surveillance via the ARF-p53 pathway Genes & Dev., October 1, 1998; 12(19): 2984 - 2991. [Full Text]
|
|
|
|
|
|
M. Florio, M.-C. Hernandez, H. Yang, H.-K. Shu, J. L. Cleveland, and M. A. Israel Id2 Promotes Apoptosis by a Novel Mechanism Independent of Dimerization to Basic Helix-Loop-Helix Factors Mol. Cell. Biol., September 1, 1998; 18(9): 5435 - 5444. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Evan and T. Littlewood A Matter of Life and Cell Death Science, August 28, 1998; 281(5381): 1317 - 1322. [Abstract] [Full Text]
|
|
|
|
|
|
A. M. Pierce, I. B. Gimenez-Conti, R. Schneider-Broussard, L. A. Martinez, C. J. Conti, and D. G. Johnson Increased E2F1 activity induces skin tumors in mice heterozygous and nullizygous for p53 PNAS, July 21, 1998; 95(15): 8858 - 8863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Ronco, A. Y. Karpova, M. Vidal, and P. M. Howley Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity Genes & Dev., July 1, 1998; 12(13): 2061 - 2072. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. M. Fimia, V. Gottifredi, B. Bellei, M. R. Ricciardi, A. Tafuri, P. Amati, and R. Maione The Activity of Differentiation Factors Induces Apoptosis in Polyomavirus Large T-Expressing Myoblasts Mol. Biol. Cell, June 1, 1998; 9(6): 1449 - 1463. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. R. Bennett, K. Macdonald, S.-W. Chan, J. J. Boyle, and P. L. Weissberg Cooperative Interactions Between RB and p53 Regulate Cell Proliferation, Cell Senescence, and Apoptosis in Human Vascular Smooth Muscle Cells From Atherosclerotic Plaques Circ. Res., April 6, 1998; 82(6): 704 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Conti, G. Rainaldi, P. Matarrese, B. Varano, R. Rivabene, S. Columba, A. Sato, F. Belardelli, W. Malorni, and S. Gessani The HIV-1 vpr Protein Acts as a Negative Regulator of Apoptosis in a Human Lymphoblastoid T Cell Line: Possible Implications for the Pathogenesis of AIDS J. Exp. Med., February 2, 1998; 187(3): 403 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ishizaki, M. D. Jacobson, and M. C. Raff A Role for Caspases in Lens Fiber Differentiation J. Cell Biol., January 12, 1998; 140(1): 153 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. LeCouter, B Kablar, P. Whyte, C Ying, and M. Rudnicki Strain-dependent embryonic lethality in mice lacking the retinoblastoma-related p130 gene Development, January 12, 1998; 125(23): 4669 - 4679. [Abstract] [PDF]
|
|
|
|
|
|
T Endo and B Nadal-Ginard Reversal of myogenic terminal differentiation by SV40 large T antigen results in mitosis and apoptosis J. Cell Sci., January 4, 1998; 111(8): 1081 - 1093. [Abstract] [PDF]
|
|
|
|
|
|
M. V. Kato, H. Sato, M. Nagayoshi, and Y. Ikawa Upregulation of the Elongation Factor-1alpha Gene by p53 in Association With Death of an Erythroleukemic Cell Line Blood, August 15, 1997; 90(4): 1373 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
