A role for the Adenomatous Polyposis Coli protein in chromosome segregation

Mutations in the Adenomatous Polyposis Coli (APC) gene are responsible for familial colon cancer and also occur in the early stages of sporadic colon cancer(1). APC functions in the Wnt signalling pathway to regulate the degr adation of beta -catenin (reviewed in refs 1-3). APC also binds to and stab ilizes microtubules in viva and in vitro(4), localizes to clusters at the e nds of microtubules near the plasma membrane of interphase cells(5,6), and is an important regulator of cytoskeletal function(7,8). Here we show that cells carrying a truncated APC gene (Min)(9) are defective in chromosome se gregation. Moreover during mitosis, APC localizes to the ends of microtubul es embedded in kinetochores and forms a complex with the checkpoint protein s Bub1 and Bub3, In vitro, APC is a high-affinity substrate for Pub kinases . Our data are consistent with a role for APC in kinetochore-microtubule at tachment and suggest that truncations in APC that eliminate microtubule bin ding may contribute to chromosomal instability in cancer cells(10).