The F-box protein β-TrCP promotes ubiquitination of TRF1 and regulates the ALT-associated PML bodies formation in U2OS cells.

The telomeric repeat binding protein 1 (TRF1) is a major factor of the mammalian telosome/shelterin and negatively regulates telomere length by inhibiting access of telomerase at telomere termini in telomerase-positive cells. In telomerase-negative cancer cells, TRF1 also plays a critical role in the mechanism called alternative lengthening of telomeres (ALT) and is essential for formation of the ALT-associated PML bodies (APBs). It was reported that TRF1 can be degraded by the ubiquitin-proteasome pathway, involving in two regulation factors, Fbx4 and RLIM. Here, we reported that β-TrCP1, a member of the F-box family protein with ubiquitin ligase activity, is a novel TRF1-associating protein. β-TrCP1 interacts with TRF1 in vivo and in vitro and promotes its ubiquitination. Overexpression of β-TrCP1 reduces endogenous TRF1 protein levels, while inhibition of β-TrCP1 by siRNA stabilizes TRF1. Moreover, we found that β-TrCP1 is essential for regulation of promyelocytic leukemia body recruitment of TRF1 in U2OS cells. These results reveal that β-TrCP1 is involved in the negative regulation of TRF1 and represents a new pathway for APB formation in telomerase-negative cells.