Palbociclib activates the proteasome indirectly and reduces the association of ECM29 with the proteasome Palbociclib activates the proteasome indirectly.

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Palbociclib activates the proteasome indirectly and reduces the association of ECM29 with the proteasome Palbociclib activates the proteasome indirectly and reduces the association of ECM29 with the proteasome In vitro 20S proteasome activity assay with peptide substrates in the presence of 5 μM palbociclib or 10 nM bortezomib shows that palbociclib does not inhibit the proteasome directly (n = 3).Proteasome activity levels, as measured by Me4BodipyFL‐Ahx3Leu3VS probe, after siRNA‐mediated CDK4/6 knockdown and palbociclib in HeLa and MCF7 cells (n = 3–4). Knockdown efficiency was analyzed by Western blotting. These data indicate that proteasome activation is likely independent of CDK4/6 inhibition through palbociclib.Same as (B), but siRNAs targeted RB1 in HeLa cells (n = 3).Workflow schematic of the mass spectrometry‐based analysis of proteasome activation mechanism. Palbociclib (10 μM) and Torin‐1 (1 μM) treatments of MCF7 cells lasted 4 h (n = 3).Volcano plots showing abundance changes and statistical significances for proteasome subunit levels in palbociclib‐ (left) and Torin‐1 (right)‐treated MCF7 cells. Proteasomes show significantly reduced levels of ECM29 upon palbociclib treatment.Data information: In panels (A–C), data are presented as means ± SD; each n represents an individual biological replicate. P‐value for panel (C) was determined by two‐tailed Student's t‐test; ns depicts not significant (P > 0.05).Source data are available online for this figure. Teemu P Miettinen et al. EMBO J. 2018;embj.201798359 © as stated in the article, figure or figure legend