Nature·· 6 hours agoPickScore82
WEE1 opposes APC/CCDH1 activity to promote S phase entry.
In brief
WEE1 phosphorylates CDH1 (FZR1) to inhibit APC/CCDH1 activity, promoting cell cycle entry from G0 into S phase. Loss of WEE1 function during G0/G1 delays S phase entry, impairs the G1/S transition, and causes abnormal S phase accumulation of p21Cip1/Kip1 and p21-dependent G2 arrest. Reduced APC/CCDH1 or p21 expression sensitizes cells to acute WEE1 inhibition, and both pathways are downregulated in cells with acquired resistance to WEE1 inhibitors.
Why it matters
WEE1 promotes G0-to-S phase entry by opposing APC/CCDH1, providing cell cycle context for WEE1 inhibitor efficacy and resistance in TP53-wild-type tumours.
Source: Nature · doi.org