UV-induced binding of ING1 to PCNA regulates the induction of apoptosis
| Autor: | François-Michel Boisvert, Karl Riabowol, Diego Vieyra, David P. Bazett-Jones, Dallan Young, Paul Bonnefin, Michelle S. Scott |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
DNA Replication
DNA Repair HMG-box Ultraviolet Rays DNA damage DNA repair RNA Splicing Gene Expression Apoptosis Cell Cycle Proteins DNA polymerase delta Cell Line RFC2 Replication factor C Proliferating Cell Nuclear Antigen Humans Genes Tumor Suppressor Cell Nucleus chemistry.chemical_classification DNA ligase Binding Sites biology Tumor Suppressor Proteins Intracellular Signaling Peptides and Proteins Nuclear Proteins Proteins Cell Biology Fibroblasts Molecular biology Protein Structure Tertiary Proliferating cell nuclear antigen Cell biology DNA-Binding Proteins chemistry biology.protein Inhibitor of Growth Protein 1 Protein Binding |
| Zdroj: | Journal of Cell Science. 114:3455-3462 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.114.19.3455 |
| Popis: | Previous studies have shown that UV-induced binding of p21(WAF1) to PCNA through the PCNA-interacting protein (PIP) domain in p21(WAF1) promotes a switch from DNA replication to DNA repair by altering the PCNA protein complex. Here we show that the p33(ING1b) isoform of the ING1 candidate tumour suppressor contains a PIP domain. UV rapidly induces p33(ING1b) to bind PCNA competitively through this domain, a motif also found in DNA ligase, the DNA repair-associated FEN1 and XPG exo/endonucleases, and DNA methyltransferase. Interaction of p33(ING1b) with PCNA occurs between a significant proportion of ING1 and PCNA, increases more than tenfold in response to UV and is specifically inhibited by overexpression of p21(WAF1), but not by p16(MTS1), which has no PIP sequence. In contrast to wild-type p33(ING1b), ING1 PIP mutants that do not bind PCNA do not induce apoptosis, but protect cells from UV-induced apoptosis, suggesting a role for this PCNA-p33(ING1b) interaction in eliminating UV-damaged cells through programmed cell death. These data indicate that ING1 competitively binds PCNA through a site used by growth regulatory and DNA damage proteins, and may contribute to regulating the switch from DNA replication to DNA repair by altering the composition of the PCNA protein complex. |
| Databáze: | OpenAIRE |
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