DOWN-REGULATION OF ACTIN GENES PRECEDES MICROFILAMENT NETWORK DISRUPTION AND ACTIN CLEAVAGE DURING P53-MEDIATED APOPTOSIS

Inactivation of Simian Virus 40 large T antigen, in cells immortalized with conditional mutants, leads to activation of p53 and apoptosis. W e used the mRNA differential display method to identify genes differen tially expressed during this process. We found that steady-state level s of mRNA for cytoplasmic actins decreased early during apoptosis, We also showed that, although the steady-state level of the corresponding proteins is not profoundly affected, they are substrates for an inter leukin 1-beta converting enzyme (ICE)-like protease activated during t he process, However, only a very small fraction of actin is proteolyse d during the early stages of apoptosis. The microfilament network is a ffected and non polymerized actin accumulates in apoptotic bodies afte r the decrease of mRNA levels, but before a significant amount of acti n is cleaved, This suggests that down-regulation of actin genes may be involved in microfilament rearrangements during p53-mediated apoptosi s.