S. Den-heuvel and N. J. Dyson, Conserved functions of the pRB and E2F families, Nat Rev Mol Cell Biol, vol.9, pp.713-737, 2008.

W. Du, M. Vidal, J. E. Xie, and N. Dyson, RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila, Genes Dev, vol.10, pp.1206-1224, 1996.

O. Stevaux, D. Dimova, M. V. Frolov, B. Taylor-harding, M. E. Dyson et al., Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2, Embo J, vol.21, pp.4927-4964, 2002.

S. Xin, L. Weng, J. Xu, and W. Du, The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth, Development, vol.129, pp.1345-56, 2002.

E. Y. Lee, C. Y. Chang, N. Hu, Y. C. Wang, C. C. Lai et al., Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis, Nature, vol.359, pp.288-94, 1992.

T. Jacks, A. Fazeli, E. M. Schmitt, R. T. Bronson, M. A. Goodell et al., Effects of an Rb mutation in the mouse, Nature, vol.359, pp.295-300, 1992.

A. De-bruin, L. Wu, H. I. Saavedra, P. Wilson, Y. Yang et al., Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rbdeficient mice, Proc Natl Acad Sci U S A, vol.100, pp.6546-51, 2003.

N. A. Mason-richie, M. J. Mistry, C. A. Gettler, A. Elayyadi, and K. A. Wikenheiser-brokamp,

, Retinoblastoma function is essential for establishing lung epithelial quiescence after injury, Cancer Res, vol.68, pp.4068-76, 2008.

S. Ruiz, M. Santos, C. Segrelles, H. Leis, J. L. Jorcano et al., Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis, Development, vol.131, pp.2737-2785, 2004.

Y. Wang, S. K. Ray, P. W. Hinds, and A. B. Leiter, The retinoblastoma protein, RB, is required for gastrointestinal endocrine cells to exit the cell cycle, but not for hormone expression, Dev Biol, vol.311, pp.478-86, 2007.

A. Almasan, Y. Yin, R. E. Kelly, E. Y. Lee, A. Bradley et al., Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis, Proc Natl Acad Sci U S A, vol.92, pp.5436-5476, 1995.

K. E. Knudsen, D. Booth, S. Naderi, Z. Sever-chroneos, A. F. Fribourg et al., RB-dependent S-phase response to DNA damage, Mol Cell Biol, vol.20, pp.7751-63, 2000.

M. S. Huh, M. H. Parker, A. Scime, R. Parks, and M. A. Rudnicki, Rb is required for progression through myogenic differentiation but not maintenance of terminal differentiation, J Cell Biol, vol.166, pp.865-76, 2004.

W. Du and N. Dyson, The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis, Embo J, vol.18, pp.916-941, 1999.

M. Duman-scheel, L. A. Johnston, and W. Du, Repression of dMyc expression by Wingless promotes Rbf-induced G1 arrest in the presumptive Drosophila wing margin, Proc Natl Acad Sci U S A, vol.101, pp.3857-62, 2004.

N. S. Moon, M. V. Frolov, E. J. Kwon, D. Stefano, L. Dimova et al., Drosophila E2F1 has context-specific pro-and antiapoptotic properties during development, Dev Cell, vol.9, pp.463-75, 2005.

N. S. Moon, D. Stefano, L. Dyson, and N. , A gradient of epidermal growth factor receptor signaling determines the sensitivity of rbf1 mutant cells to E2F-dependent apoptosis, Mol Cell Biol, vol.26, pp.7601-7616, 2006.

L. C. Firth and N. E. Baker, Extracellular signals responsible for spatially regulated proliferation in the differentiating Drosophila eye, Dev Cell, vol.8, pp.541-51, 2005.

C. Bowen, S. Spiegel, and E. P. Gelmann, Radiation-induced apoptosis mediated by retinoblastoma protein, Cancer Res, vol.58, pp.3275-81, 1998.

K. Araki, S. M. Ahmad, G. Li, D. A. Bray, J. Saito et al., Retinoblastoma RB94 enhances radiation treatment of head and neck squamous cell carcinoma, Clin Cancer Res, vol.14, pp.3514-3523, 2008.

J. K. Hsieh, F. S. Chan, D. J. O'connor, S. Mittnacht, S. Zhong et al., RB regulates the stability and the apoptotic function of p53 via MDM2, Mol Cell, vol.3, pp.181-93, 1999.

K. E. Knudsen, E. Weber, K. C. Arden, W. K. Cavenee, J. R. Feramisco et al., The retinoblastoma tumor suppressor inhibits cellular proliferation through two distinct mechanisms: inhibition of cell cycle progression and induction of cell death, Oncogene, vol.18, pp.5239-5284, 1999.

X. Zhao and M. L. Day, RB activation and repression of C-MYC transcription precede apoptosis of human prostate epithelial cells, Urology, vol.57, pp.860-865, 2001.

C. Lemaire, N. Godefroy, I. Costina-parvu, V. Rincheval, F. Renaud et al., Caspase-9 can antagonize p53-induced apoptosis by generating a p76(Rb) truncated form of Rb, Oncogene, vol.24, pp.3297-308, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00101331

A. Ianari, T. Natale, E. Calo, E. Ferretti, E. Alesse et al., Proapoptotic function of the retinoblastoma tumor suppressor protein, Cancer Cell, vol.15, pp.184-94, 2009.

S. A. Datar, H. W. Jacobs, A. F. De-la-cruz, C. F. Lehner, and B. A. Edgar, The Drosophila cyclin D-Cdk4 complex promotes cellular growth, EMBO J, vol.19, pp.4543-54, 2000.

L. Weng, C. Zhu, J. Xu, and W. Du, Critical role of active repression by E2F and Rb proteins in endoreplication during Drosophila development, EMBO J, vol.22, pp.3865-75, 2003.

T. P. Neufeld, A. F. De-la-cruz, L. A. Johnston, and B. A. Edgar, Coordination of growth and cell division in the Drosophila wing, Cell, vol.93, pp.1183-93, 1998.

B. A. Hay, T. Wolff, and G. M. Rubin, Expression of baculovirus P35 prevents cell death in Drosophila, Development, vol.120, pp.2121-2130, 1994.

S. Gaumer, I. Guenal, S. Brun, L. Theodore, and B. Mignotte, Bcl-2 and Bax mammalian regulators of apoptosis are functional in Drosophila, Cell Death Differ, vol.7, pp.804-818, 2000.

L. M. Quinn, L. Dorstyn, K. Mills, P. A. Colussi, P. Chen et al.,

H. Richardson, An essential role for the caspase dronc in developmentally programmed cell death in Drosophila, J Biol Chem, vol.275, pp.40416-40440, 2000.

P. Meier, J. Silke, S. J. Leevers, and G. I. Evan, The Drosophila caspase DRONC is regulated by DIAP1, EMBO J, vol.19, pp.598-611, 2000.

D. Xu, Y. Li, M. Arcaro, M. Lackey, and A. Bergmann, The CARD-carrying caspase Dronc is essential for most, but not all, developmental cell death in Drosophila, Development, vol.132, pp.2125-2159, 2005.

M. Asano, J. R. Nevins, and R. P. Wharton, Ectopic E2F expression induces S phase and apoptosis in Drosophila imaginal discs, Genes Dev, vol.10, pp.1422-1454, 1996.

W. Du, J. E. Xie, and N. Dyson, Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye, Embo J, vol.15, pp.3684-92, 1996.

S. Jin, S. Martinek, W. S. Joo, J. R. Wortman, N. Mirkovic et al., Identification and characterization of a p53 homologue in Drosophila melanogaster, Proc Natl Acad Sci U S A, vol.97, pp.7301-7307, 2000.

G. Morata and P. Ripoll, Minutes: mutants of drosophila autonomously affecting cell division rate

, Dev Biol, vol.42, pp.211-232, 1975.

E. Moreno, Is cell competition relevant to cancer?, Nat Rev Cancer, vol.8, pp.141-148, 2008.

N. Godefroy, C. Lemaire, B. Mignotte, and J. L. Vayssiere, p53 and Retinoblastoma protein (pRb): a complex network of interactions, Apoptosis, vol.11, pp.659-61, 2006.

C. B. Brachmann, O. W. Jassim, B. D. Wachsmuth, and R. L. Cagan, The Drosophila bcl-2 family member dBorg-1 functions in the apoptotic response to UV-irradiation, Curr Biol, vol.10, pp.547-50, 2000.

P. A. Colussi, L. M. Quinn, D. C. Huang, M. Coombe, S. H. Read et al., Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery, J Cell Biol, vol.148, pp.703-717, 2000.

T. Igaki, H. Kanuka, N. Inohara, K. Sawamoto, G. Nunez et al.,

, Drosophila member of the Bcl-2/CED-9 family that promotes cell death, Proc Natl Acad Sci U S A, vol.97, pp.662-669, 2000.

H. Zhang, W. Holzgreve, D. Geyter, and C. , Evolutionarily conserved Bok proteins in the Bcl-2 family, FEBS Lett, vol.480, pp.311-314, 2000.

H. Zhang, Q. Huang, N. Ke, S. Matsuyama, B. Hammock et al., Drosophila proapoptotic Bcl-2/Bax homologue reveals evolutionary conservation of cell death mechanisms, J Biol Chem, vol.275, pp.27303-27309, 2000.

S. Decary, J. T. Decesse, V. Ogryzko, J. C. Reed, I. Naguibneva et al., 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, vol.22, pp.7877-88, 2002.

Y. Haupt, S. Rowan, and M. Oren, p53-mediated apoptosis in HeLa cells can be overcome by excess pRB, Oncogene, vol.10, pp.1563-71, 1995.

M. M. Lipinski, K. F. Macleod, B. O. Williams, T. L. Mullaney, D. Crowley et al., Cellautonomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system, EMBO J, vol.20, pp.3402-3415, 2001.

A. Brook, J. E. Xie, W. Du, and N. Dyson, Requirements for dE2F function in proliferating cells and in post-mitotic differentiating cells, EMBO J, vol.15, pp.3676-83, 1996.

M. Ollmann, L. M. Young, D. Como, C. J. Karim, F. Belvin et al.,

, Drosophila p53 is a structural and functional homolog of the tumor suppressor p53, Cell, vol.101, pp.91-101, 2000.

S. Brun, V. Rincheval, S. Gaumer, B. Mignotte, and I. Guenal, reaper and bax initiate two different apoptotic pathways affecting mitochondria and antagonized by bcl-2 in Drosophila, Oncogene, vol.21, pp.6458-70, 2002.

, A-D) Adult structures of control genotypes: vg-Gal4/+ wing (A), ey-Gal4/+ eyes (B), elav-Gal4/+ eyes (C), and elav-Gal4/+ eye photoreceptors (D). (E-H) Adult phenotypes of RBF expressing flies: vg-Gal4/+;UAS-RBF/+ wing (E) (asterisks indicate notches in the margin), ey-Gal4/+;UAS-RBF/+ eyes (F), elav-Gal4/+;UAS-RBF/+ eyes (G), and elav-Gal4/+;UAS-RBF/+ photoreceptors (H), RBF expression induces apoptosis only in proliferating cells and not in post-mitotic cells. RBF expression is driven in proliferating tissues using vg-Gal4 and ey-Gal4, and in post-mitotic cells using elav-Gal4

, Control imaginal discs: vg-Gal4/+ wing disc (I), ey-Gal4/+ (J) and elav-Gal4/+ (K) eye discs. (L-N) Imaginal discs of RBF expressing larvae: vg-Gal4/+;UAS-RBF/+ wing disc (L)

E. Rbf/+-(m), N) eyes discs. White bright patches corresponding to apoptotic cells are principally observed in (L) and (M). (O) Detection of RBF protein in third instar