Coupling caspase cleavage and ubiquitin-proteasome-dependent degradation of SSRP1 during apoptosis.
Structure-specific recognition protein (SSRP1) is an 87 kDa protein that heterodimerizes with Spt16 to form FACT, a complex initially shown to facilitate chromatin transcription. Despite its crucial roles in transcription and replication, little is known about the dynamics of FACT turnover in vivo. Here, we show that SSRP1 is cleaved during apoptosis by caspase 3 and/or 7 at the DQHD(450) site. Analysis of the resulting fragments suggests that cleavage of SSRP1 generates a truncated, chromatin-associated form of FACT. Furthermore, the N-terminal product is stabilized by proteasome inhibitors and ubiquitylated in cells, suggesting degradation through the ubiquitin-proteasome pathway. These results demonstrate that SSRP1 degradation during apoptosis is a two-step process coupling caspase cleavage and ubiquitin-dependent proteolysis.
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239, USA.
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D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006207:Half-Life; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D035602:Transcriptional Elongation Factors / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000378:metabolism*
D002843:Chromatin; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D007976:Leupeptins; D010446:Peptide Fragments; C073537:SSRP1 protein, human; D035602:Transcriptional Elongation Factors; D025801:Ubiquitin; D053148:Caspase 3; D053179:Caspase 7; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde