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DTL / CDT2
denticleless E3 ubiquitin protein ligase homolog (Drosophila)
Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1) and SETD8. CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. SETD8 degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis.
| Gene Name: | denticleless E3 ubiquitin protein ligase homolog (Drosophila) |
| Synonyms: | DTL, Denticleless protein homolog, CDT2, DCAF2, CDW1, Denticleless homolog, L2DTL, RAMP |
| Target Sequences: | NM_016448 NP_057532.3 Q9NZJ0 |
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