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Docking of a specialized PIP box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2
| Content Provider | PubMed Central |
|---|---|
| Author | Havens, Courtney G. Walter, Johannes C. |
| Copyright Year | 2009 |
| Abstract | Substrates of the E3 ubiquitin ligase CRL4Cdt2, including Cdt1 and p21, contain a PCNA-binding motif called a PIP box. Upon binding of the PIP box to PCNA on chromatin, CRL4Cdt2 is recruited and the substrate is ubiquitylated. Importantly, a PIP box cannot be sufficient for destruction, as most PIP box proteins are stable. Using Xenopus egg extracts, we identify two sequence elements in CRL4Cdt2 substrates that promote their proteolysis: a specialized PIP box which confers exceptionally efficient PCNA binding, and a basic amino acid four residues downstream of the PIP box, which recruits CRL4Cdt2 to the substrate-PCNA complex. We also identify two mechanisms which couple CRL4Cdt2-dependent proteolysis to the chromatin-bound form of PCNA, insuring that this proteolysis pathway is active only in S phase or after DNA damage. Thus, CRL4Cdt2 recognizes an unusual degron, which is assembled specifically on chromatin via the binding of a specialized PIP box to PCNA. |
| Related Links | http://dx.doi.org/10.1016/j.molcel.2009.05.012 |
| Starting Page | 93 |
| File Format | |
| ISSN | 10974164 |
| e-ISSN | 10974164 |
| Journal | Molecular cell |
| Issue Number | 1 |
| Volume Number | 35 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
