Fig. 7: Control of c-myc and Cip/Kip levels for the maintenance of quiescence in differentiated cells. | Nature Communications

Fig. 7: Control of c-myc and Cip/Kip levels for the maintenance of quiescence in differentiated cells.

From: Non-canonical pathway for Rb inactivation and external signaling coordinate cell-cycle entry without CDK4/6 activity

Fig. 7

a Percentage of S-phase cells in PLB-985, PC-12, and OP-9 cells after differentiation for the indicated time. Data are shown as mean ± SD (n = 3 biological replicates). Asterisks indicate significant differences in the two-tailed unpaired t-test (PC-12 cells) or one-way ANOVA test (PLB-985 and OP-9 cells) (*p ≤ 0.05; **p ≤ 0.001; ***p ≤ 0.0001). b Percentage of neurite bearing PC-12 cells before and after one-day differentiation. Data are shown as mean ± SD (n = 3 biological replicates). Asterisks indicate significant differences in the two-tailed unpaired t-test (*p ≤ 0.05). c Percentage of high-PPARγ expressing OP-9 cells. Data are shown as mean ± SD (n = 3 biological replicates). Asterisks indicate significant differences in the one-way ANOVA test (*p ≤ 0.05; **p ≤ 0.001). d Immunoblot showing Rb, c-Myc, p21, p27, and GAPDH expression before and after differentiation. FPR1, SYN1, and PPARγ are cell differentiation markers. e Percentage of S-phase OP-9 cells expressing a doxycycline-inducible c-Myc construct. After 6 days of differentiation, cells were treated with palbociclib (1 µM) and EdU (10 µM) + DMSO or doxycycline (5 µM) for 72 h. Data are shown as mean ± SD (n = 3 biological replicates). Asterisks indicate significant differences in the two-tailed unpaired t-test (*p ≤ 0.05). f Schematic diagram illustrating CDK4/6-independent cell-cycle entry by multiple steps: (1) reduction in Rb-protein levels, (2) c-Myc-mediated amplification of E2F activity, and (3) inhibition of CDK2 activity by Cip/Kip.

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