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. We used the mRNA differential display method to identify genes differentially expressed during this process. We found that steady-state levels 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 interleukin 1-beta converting enzyme (ICE)-like protease activated during the process. However, only a very small fraction of actin is proteolysed during the early stages of apoptosis. The microfilament network is affected and non polymerized actin accumulates in apoptotic bodies after the decrease of mRNA levels, but before a significant amount of actin is cleaved. This suggests that down-regulation of actin genes may be involved in microfilament rearrangements during p53-mediated apoptosis.
Guénal
I
I
Centre de Génétique Moléculaire, UPR 9061 du CNRS, Gif-sur-Yvette, France.
Risler
Y
Y
Mignotte
B
B
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D020170:Caspase 1; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D051381:Rats; D013379:Substrate Specificity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000199:Actins; D016159:Tumor Suppressor Protein p53; D003546:Cysteine Endopeptidases; D020170:Caspase 1