Triggering of p73-dependent apoptosis in osteosarcoma is under the control of E2Fs–pRb2/p130 complexes

Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implications for pathogenesis and therapeutic approach

“…The authors suggest that the additional mutations that are present in all retinoblastomas may interrupt signals that normally would induce apoptosis when RB1/p105 is absent. Actually, our previous data (La Sala et al, 2003) were obtained in the Hos osteosarcoma cell line, which presents RB1/p105 biallelic deletion, and osteosarcoma is the most common neoplasm secondary to retinoblastoma (Eng et al, 1993). Therefore, RB2/p130 inactivation could contribute to retinoblastoma genesis, depriving the cell of a further tool to control proliferation and to induce the elimination of inappropriate cells by a p73-dependent proapoptotic pathway.…”

“…At the same time pRb2/p130 expression level was maximum. Recently, we have shown that pRb2/p130 is able to induce p53-independent apoptosis by controlling the transcription of p73 through the binding of activating pRb2/p130-E2F1-p300 or repressive pRb2/p130-E2F4-HDAC1 multimolecular complexes on p73 promoter in osteosarcoma (La Sala et al, 2003). Here we show that an increase in the expression of pRb2/p130 is concomitant with upregulation of E2F1 and p73 but not of E2F4, suggesting that activation of the proapoptotic pathway could play a preponderant role in determining growth cell arrest.…”

“…pRb1/p105 functions are shared by two homologous proteins, pRb2/p130 and p107, so that the three of them are referred to as retinoblastoma family proteins (pRBs) (Cinti and Giordano, 2000). In particular, RB2/p130 gene has been found mutated or functionally inactivated in many tumors and its role in controlling p53-independent apoptotic response has been elucidated recently (La Sala et al, 2003). Interestingly, we reported recently (Bellan et al, 2002) that, in some sporadic retinoblastomas, also the expression of pRb2/p130 is impaired and its loss of expression correlates with low apoptotic index, suggesting that in sporadic retinoblastoma also RB2/p130 gene could be mutated or functionally inactivated.…”

“…Western blot analysis showed that the effects of the de-methylating treatment on cell growth were concomitant with increased expression of endogenous pRb2/p130 with respect to the control obtained after 96 h cell culture (Figure 3b). Recently, we reported that pRb2/p130 is involved in p53-independent apoptotic response via a p73 pathway (La Sala et al, 2003). Therefore, we evaluated whether the apoptotic response evidenced by FACS analysis is mediated by this same pathway by analysing the expression level of E2F1 and p73 as a function of the treatment period.…”

Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological crosstalk in human corneal and conjunctival epithelial cells

“…19 Recently, we have suggested a functional interaction between pRb2/p130 and chromatin modifying enzymes to control the transcription of p73 and ER-a genes. 20,21 Here, we show that pRb2/p130 and Rb1/p105, but not p107, interact with PAI-2 in both the cytoplasm and nucleus of normal primary human corneal and conjunctival epithelial cell cultures. Moreover, we reported that, in the same cell lines, pRb2/p130, E2F5, PAI-2 and the chromatin modifying enzymes DNA methyltransferase 1 (DNMT1), histone deacetylase 1 (HDAC1) and histone methyltransferase (SUV39H1) simultaneously bind, in vivo, the same region on the PAI-2 proximal promoter.…”