p53 facilitates pRb cleavage in IL-3-deprived cells: novel pro-apoptotic activity of p53

Gottlieb, Eyal; Oren, Moshe
July 1998
EMBO Journal;7/1/98, Vol. 17 Issue 13, p3587
Academic Journal
In the interleukin-3 (IL-3)-dependent lymphoid cell line DA-1, functional p53 is required for efficient apoptosis in response to IL-3 withdrawal. Activation of p53 in these cells, by either DNA damage or p53 overexpression, results in a vital growth arrest in the presence of IL-3 and in accelerated apoptosis in its absence. Thus, IL-3 can control the choice between p53-dependent cell-cycle arrest and apoptosis. Here we report that the cross-talk between p53 and IL-3 involves joint control of pRb cleavage and degradation. Depletion of IL-3 results in caspase-mediated pRb cleavage, occurring preferentially within cells which express functional p53. Moreover, pRb can be cleaved efficiently by extracts prepared from DA-1 cells but not from their derivatives which lack p53 function. Inactivation of pRb through expression of the human papillomavirus (HPV) E7 oncogene overrides the effect of IL-3 in a p53-dependent manner. Our data suggest a novel role for p53 in the regulation of cell death and a novel mechanism for the cooperation between p53 and survival factor deprivation. Thus, p53 makes cells permissive to pRb cleavage, probably by controlling the potential activity of a pRb-cleaving caspase, whereas IL-3 withdrawal provides signals that turn on this potential activity and lead to the actual cleavage and subsequent degradation of pRb. Elimination of a presumptive anti-apoptotic effect of pRb may then facilitate conversion of p53-mediated growth arrest into apoptosis.


Related Articles

  • UP-REGULATION OF CELL CYCLE-ASSOCIATED GENES BY P53 IN APOPTOSIS OF AN ERYTHROLEUKEMIC CELL LINE. Kato, Mitsuo V.; Sato, Hiromi; Anzai, Hiroko; Nagayoshi, Mariko; Ikawa, Yoji // Leukemia (08876924);Apr97 Supplement 3, Vol. 11, p389 

    A murine erythroleukemic cell line (1-2-3) which expresses only the temperature-sensitive mutant p53 gene (Ata-to-Val substitution at codon 135) was established. When these cells were cultured at 32°C, the growth rate was reduced significantly and DNA fragmentation, a typical character of...

  • Apoptotic effect of ethyl-4-isothiocyanatobutanoate is associated with DNA damage, proteasomal activity and induction of p53 and p21cip1/waf1. Bodo, Juraj; Jakubikova, Jana; Chalupa, Ivan; Bartosova, Zdena; Horakova, Katarina; Floch, Lubomir; Sedlak, Jan // Apoptosis;Aug2006, Vol. 11 Issue 8, p1299 

    The effect of synthetic isothiocyanate ethyl-4-isothiocyanatobutanoate (E-4IB) on survival of mismatch repair-proficient TK6 and -deficient MT1 cell lines as well as the influence of proteasomal inhibitor MG132, caspase inhibitor Z-VAD-fmk, and ATM inhibitor caffeine on E-4IB modulation of cell...

  • p53 protein regulates the effects of amifostine on apoptosis, cell cycle progression, and cytoprotection. Lee, E J; Gerhold, M; Palmer, M W; Christen, R D // British Journal of Cancer;3/10/2003, Vol. 88 Issue 5, p754 

    To determine the role of p53 protein on the cellular effects of amifostine, we used molecularly engineered HCT116 colon cancer cells in which the p53 gene was inactivated by targeted homologous recombination or p53 protein was degraded by high-level expression of papillomavirus E6 protein,...

  • Human ΔNp73 regulates a dominant negative feedback loop for TAp73 and p53. Grob, T J; Novak, U; Maisse, C; Barcaroli, D; Lüthi, A U; Pirnia, F; Hügli, B; Graber, H U; De Laurenzi, V; Fey, M F; Melino, G; Tobler, A // Cell Death & Differentiation;Dec2001, Vol. 8 Issue 12, p1213 

    Inactivation of the tumour suppressor p53 is the most common defect in cancer cells, p53 is a sequence specific transcription factor that is activated in response to various forms of genotoxic stress to induce cell cycle arrest and apoptosis. Induction of p53 is subjected to complex and strict...

  • Ectopic expression of human p53 inhibits entry into S phase and induces apoptosis in the Drosophila eye imaginal disc. Yamaguchi, Masamitsu; Hirose, Fumiko; Inoue, Yoshihiro H; Shiraki, Michina; Hayashi, Yuko; Nishi, Yoshimi; Matsukage, Akio // Oncogene;11/18/99, Vol. 18 Issue 48, p6767 

    Transgenic flies in which ectopic expression of human p53 was targeted to the Drosophila eye imaginal disc were established. On sectioning of adult fly eyes which displayed a severe rough eye phenotype, most ommatidia were found to be fused and irregular shapes of rabdomeres were observed. In...

  • A human papillomavirus type 18 E6/E7 transgene sensitizes mouse lens cells to human wild-type p53-mediated apoptosis. Nakamura, Takafumi; Williams-Simons, Lisa; Westphal, Heiner // Oncogene;6/26/97, Vol. 14 Issue 25, p2991 

    We have studied the concerted action of factors that influence the balance between cell proliferation and cell death in the developing lens of transgenic mice. We show that a human papillomavirus type 18 (HPV18) E6/E7 transgene that predominantly expresses the viral E7 gene product triggers...

  • Papillomavirus E2 induces p53-independent apoptosis in HeLa cells. Desaintes, Christian; Goyat, Sylvain; Garbay, Serge; Yaniv, Moshe; Thierry, Françoise // Oncogene;8/12/99, Vol. 18 Issue 32, p4538 

    We have previously shown that expression of the papillomavirus E2 protein in HeLa cells induces p53 accumulation and causes both cell cycle arrest and apoptosis. In contrast to growth arrest, onset of apoptosis was not correlated with an increase of p53 transcriptional activity. In the present...

  • MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63. Gamble, L D; Kees, U R; Tweddle, D A; Lunec, J // Oncogene;2/9/2012, Vol. 31 Issue 6, p752 

    MYCN amplification is a major biomarker of poor prognosis, occurring in 25-30% of neuroblastomas. MYCN has contradictory roles in promoting cell growth and sensitizing cells to apoptosis. We have recently shown that p53 is a direct transcriptional target of MYCN in neuroblastoma and that...

  • p53 regulates a non-apoptotic death induced by ROS. Montero, J; Dutta, C; van Bodegom, D; Weinstock, D; Letai, A // Cell Death & Differentiation;Nov2013, Vol. 20 Issue 11, p1465 

    DNA damage induced by reactive oxygen species and several chemotherapeutic agents promotes both p53 and poly (ADP-ribose) polymerase (PARP) activation. p53 activation is well known to regulate apoptotic cell death, whereas robust activation of PARP-1 has been shown to promote a necrotic cell...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics