Polycomb group protein RING1B is a direct substrate of Caspases-3 and -9.
Both Caspase-3 and Caspase-9 play critical roles in the execution of mitochondria-mediated apoptosis. Caspase-9 binds to Apaf-1 in the presence of cytochrome c and dATP/ATP, and is activated by self-cleavage. Caspase-3 is activated by cleavage of caspase-8 and caspase-9. Over hundred direct caspase-3 substrates are identified whereas only few direct caspase-9 substrates are known. Here, we demonstrate that Ring1B, a component of polycomb protein complex that plays important roles in modulating chromatin structures, is a direct substrate of active caspase-3 and caspase-9 both in vitro and in vivo. The specific cleavage sites for caspase-3 and caspase-9 were mapped to Asp(175) and Asp(208), respectively. Importantly, cleavage of Ring1B by active caspases-3 and caspase-9 triggers the redistribution of Ring1B, from exclusive nuclear localization to even distribution throughout the entire cell. The transcriptional repression activity of Ring1B was also disrupted by caspase cleavage. Our data suggest that caspases-3 and caspase-9 play novel roles in transcription by regulating polycomb protein function through direct cleaving of Ring1B.
Wong
Chung Kai
CK
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Chen
Zhengming
Z
So
Ka Lun
KL
Li
De
D
Li
Peng
P
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D014158:Transcription, Genetic / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D004268:DNA-Binding Proteins; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases; D053148:Caspase 3; D053453:Caspase 9