Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.

The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control.

Addicted to proteostasis: How KRAS-driven cancers acquire resistance to clinical KRAS inhibitors.

The development of KRAS inhibitors was a remarkable feat, yet their efficacy is limited by inevitable resistance. In the September issue of Science, Lv et al. demonstrate how KRAS-driven cancers rewire signaling to restore protein homeostasis and acquire resistance to KRAS inhibitors with implications for novel combination therapeutic strategies.