ESR1 and endometrial cancer: As shown in Figure 4c, a group of SPOP mutants (SPOP-M117V, M117I, and R121Q) displayed reduced capacity to promote ERα degradation when compared with SPOP-WT, whereas other groups did not alter ERα protein level (SPOP-E47K, E50K, G75R, P94A, and D140G) or increased ERα protein level (SPOP-S80R), suggesting that endometrial cancer-associated SPOP mutants may differentially regulate ERα stability.