FIGURE 5.

Proliferating myocytes exit the cell cycle during differentiation that is dependent on the TRAF7 ubiquitin ligase involved in downregulating Cyclin D1 expression/ activity

A: TRAF7 ubiquitin ligase polyubiquitinates NEMO and targets it for 26S degradation, when the NEMO component of the inhibitor of kB kinase (IKK) complex is degraded. B: in the studies described in the body of the text, the MYOD transcription factor depletes TRAF7 transcription and protein expression, leading to inactivation of the NF-κB activity and reduced cyclin D1, leading to exit from cell cycle and thereby driving the cells from proliferation to differentiation stage. C: the IKK complex is released from NEMO and can then phosphorylate the IκB protein (inhibitory kappa B protein) complexed with the p65 and p50 NF-κB subunits. This results in degradation of the IκB protein, allowing the p65/p50 NF-κB transcription factor to translocate to the nucleus (D) and regulate gene transcription, including Cyclin D1 critical to cell cycle and proliferation of cells. E: summary of TRAF7 activity in myocyte differentiation.