A) Immunoblot indicating neurofibromin (NF1) degradation in serum-starved NIH3T3 fibroblasts stimulated with 10% serum for the times shown. RasGAPp120 (p120) is not degraded under these conditions and is shown as a loading control.
B) Serum-starved mouse embryonic fibroblasts (MEFs) were treated with a combination of proteasome inhibitors (1uM bortezomib, 10mM MG132) or vehicle (DMSO) for 2h and then stimulated with 10% serum for the times indicated. Immunoblots of neurofibromin and RasGAPp120 are shown.
C) NIH3T3 fibroblasts were infected with a lentiviral control or a lentivirus containing an shRNA sequence directed against specific mammalian cullin genes as noted. Knock-down of cullins was confirmed by immunoblot (IB). Neurofibromin and RasGAPp120 immunoblots of serum-starved cells stimulated with 10% serum for the times indicated are shown.
D) Immunoblot of neurofibromin degradation in NIH3T3 fibroblasts expressing a control shRNA vector or distinct shRNA constructs targeting different regions of the Cul3 transcript. Cul3 depletion is confirmed by immunoblot, and RasGAPp120 levels are shown as a loading control.
E) Immunoblot of neurofibromin degradation in control or shCul3-expressing NIH3T3 fibroblasts following PKC activation (10nM PMA) for 5 min. Cul3 depletion and a RasGAPp120 loading control are also shown.