Fission yeast essential nuclear pore protein Nup211 regulates the expression of genes involved in cytokinesis.

Nuclear pore proteins control nucleocytoplasmic transport; however, certain nucleoporins play regulatory roles in activities such as transcription and chromatin organization. The fission yeast basket nucleoporin Nup211 is implicated in mRNA export and is essential for cell viability. Nup211 preferentially associates with heterochromatin, however, it is unclear whether it plays a role in regulating transcription.

BxPC3 pancreatic cancer cells express a truncated Smad4 protein upon PI3K and mTOR inhibition.

Smad4 is a critical regulator of transforming growth factor (TGF)-β signaling and is defective in numerous human cancers. In total, 30% of pancreatic cancers harbor a homozygous deletion of Smad4. The human pancreatic cancer cell line, BxPC3, has been reported to be Smad4-null due to a homozygous deletion and has been widely used as a Smad4-null model.

Suppression of AKT phosphorylation restores rapamycin-based synthetic lethality in SMAD4-defective pancreatic cancer cells.

mTOR has been implicated in survival signals for many human cancers. Rapamycin and TGF-β synergistically induce G1 cell-cycle arrest in several cell lines with intact TGF-β signaling pathway, which protects cells from the apoptotic effects of rapamycin during S-phase of the cell cycle. Thus, rapamycin is cytostatic in the presence of serum/TGF-β and cytotoxic in the absence of serum.