Proapoptotic histone H1.2 induces CASP-3 and -7 activation by forming a protein complex with CYT c, APAF-1 and CASP-9.
Cytochrome c (CYT c) is a protein that employs the caspase recruitment domain (CARD)-containing proteins APAF-1 and CASP-9 to activate effectors CASP-3 and -7. By using affinity labeling techniques and mass spectrometry analysis, we show that histone H1.2 is a regulator of caspases upon UV irradiation. We demonstrated that histone H1.2 forms a protein complex with APAF-1, CASP-9 and CYT c upon UV irradiation. In cell-free systems, we show that histone H1.2 triggers activation of CASP-3 and -7 via APAF-1 and CASP-9. We therefore conclude that upon DNA damage histone H1.2 acts as a positive regulator of apoptosome formation.
Ruiz-Vela
Antonio
A
Howard Hughes Medical Institute, Department of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA. aruiz@cnio.es
Korsmeyer
Stanley J
SJ
D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism*; D053453:Caspase 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism*; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding
D053477:Apoptotic Protease-Activating Factor 1; D006657:Histones; D045304:Cytochromes c; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9