Figure 4.

Role of ubiquitylation in MYC-driven transcription. Hypothetical model describing SKP2-mediated ubiquitylation and degradation of MYC at a MYC target gene promoter. Left: MYC (in complex with MAX) binds the promoter. SKP2 as part of an Skp1–Cullin1–F-box (SCF) E3 ligase complex is recruited to the promoter and starts ubiquitylating MYC. The 19S proteasome subcomplex, with or without the rest of the proteasome, and hypothetical ubiquitin-binding cofactors interacts with MYC via attraction to the growing ubiquitin chain. MYC also interacts with subunits of the RNA polymerase II (Pol II) complex and with positive transcription elongation factor P-TEFb; Middle: the recruited 19S complex and coactivators stimulate initiation and/or elongation of transcription. SKP2 may, as described for other transcription contexts, ubiquitylate P-TEFb and thereby contribute to transcription elongation. The ubiquitylation of MYC continues, producing longer ubiquitin chains and the 26S proteasome starts acting on MYC; Right: the proteasome degrades MYC and transcription is completed. SKP2, cofactors, P-TEFb and the proteasome dissociates and Pol II exits the promoter after the transcription termination site. A new round of transcription can initiate as newly synthesized MYC enters the promoter. See the text for further explanation.