Marcus J. C. Long#, Hong-Yu Lin#, Saba Parvez, Yi Zhao, Jesse R. Poganik, Paul Huang, and Yimon Aye*
(Original Research, #, co-first authors)
eTOC: Upregulation of β-catenin activity promotes Wnt-dependent oncogenesis. β-catenin upregulation often occurs through mutation in its N-terminus which binds β-TrCP. We show that modification of the β-catenin N-terminus also sensitizes cells to Nrf2-mediated inhibition of Wnt signaling. This acquired susceptibility may be exploitable for cancer therapy.
Marcus J. C. Long#, and Yimon Aye*
eTOC: Covalent drugs are resurging: many are recently approved and more are in clinical trials. Here Long and Aye suggest mining “first-responding cysteines” reactive to endogenous electrophiles to develop better covalent drugs. These cysteines are kinetically privileged to engage with sp2-hybridized carbon, and have unique functions that are tied in to electrophile adduction.