Limits...
Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway.

Trisciuoglio L, Bianchi ME - PLoS ONE (2009)

Bottom Line: A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering.We find that all depend directly or indirectly on caspase-3 activation.CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.

View Article: PubMed Central - PubMed

Affiliation: Chromatin Dynamics Unit, San Raffaele Scientific Institute, Milano, Italy.

ABSTRACT
A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.

Show MeSH
Cause-effect relationships in nuclear events during apoptosis.Broken lines indicate incomplete knowledge: intermediate steps might be missing, or causation is only inferred. Continuous lines indicate direct cause-effect relationships. The grey area groups events that appear interconnected downstream of caspase-3 actiavtion: histone H2AX phosphorylation, ICAD cleavage, CAD activation, DNA laddering and CAD immbilization.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2713420&req=5

pone-0006234-g008: Cause-effect relationships in nuclear events during apoptosis.Broken lines indicate incomplete knowledge: intermediate steps might be missing, or causation is only inferred. Continuous lines indicate direct cause-effect relationships. The grey area groups events that appear interconnected downstream of caspase-3 actiavtion: histone H2AX phosphorylation, ICAD cleavage, CAD activation, DNA laddering and CAD immbilization.

Mentions: Caspase-3 activation causes DNA laddering (via ICAD cleavage and CAD activation), the immobilization of CAD, and histone H2B phosphorylation (via Mst1 kinase activation) (Figure 8). Lu et al. [21] reported that, upon UV irradiation, JNK1 phosphorylates H2AX and activates caspase-3; the JNK inhibitor SP600125 or dominant negative JNK1 not only suppressed activation of JNK1 but also blocked H2AX phosphorylation and caspase-3 activation. However, the inhibition of caspase-3 did not reduce H2AX phosphorylation, leading to the suggestion that caspase-3 activation is independent from H2AX phosphorylation. In contrast to these published results, we find that in MCF-7 cells undergoing TNF-α induced apoptosis the phosphorylation of H2AX occurs only when caspase-3 is expressed and activated (Figures 4A and 8). We cannot exclude, however, that this difference is due to the specific mode of apoptosis induction (UV irradiation vs TNF-α plus cycloheximide) or the particular cell line used.


Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway.

Trisciuoglio L, Bianchi ME - PLoS ONE (2009)

Cause-effect relationships in nuclear events during apoptosis.Broken lines indicate incomplete knowledge: intermediate steps might be missing, or causation is only inferred. Continuous lines indicate direct cause-effect relationships. The grey area groups events that appear interconnected downstream of caspase-3 actiavtion: histone H2AX phosphorylation, ICAD cleavage, CAD activation, DNA laddering and CAD immbilization.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2713420&req=5

pone-0006234-g008: Cause-effect relationships in nuclear events during apoptosis.Broken lines indicate incomplete knowledge: intermediate steps might be missing, or causation is only inferred. Continuous lines indicate direct cause-effect relationships. The grey area groups events that appear interconnected downstream of caspase-3 actiavtion: histone H2AX phosphorylation, ICAD cleavage, CAD activation, DNA laddering and CAD immbilization.
Mentions: Caspase-3 activation causes DNA laddering (via ICAD cleavage and CAD activation), the immobilization of CAD, and histone H2B phosphorylation (via Mst1 kinase activation) (Figure 8). Lu et al. [21] reported that, upon UV irradiation, JNK1 phosphorylates H2AX and activates caspase-3; the JNK inhibitor SP600125 or dominant negative JNK1 not only suppressed activation of JNK1 but also blocked H2AX phosphorylation and caspase-3 activation. However, the inhibition of caspase-3 did not reduce H2AX phosphorylation, leading to the suggestion that caspase-3 activation is independent from H2AX phosphorylation. In contrast to these published results, we find that in MCF-7 cells undergoing TNF-α induced apoptosis the phosphorylation of H2AX occurs only when caspase-3 is expressed and activated (Figures 4A and 8). We cannot exclude, however, that this difference is due to the specific mode of apoptosis induction (UV irradiation vs TNF-α plus cycloheximide) or the particular cell line used.

Bottom Line: A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering.We find that all depend directly or indirectly on caspase-3 activation.CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.

View Article: PubMed Central - PubMed

Affiliation: Chromatin Dynamics Unit, San Raffaele Scientific Institute, Milano, Italy.

ABSTRACT
A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.

Show MeSH