title: The F-box protein β-TrCP promotes ubiquitination of TRF1 and regulates the ALT-associated PML bodies formation in U2OS cells.
abstract: 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.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Haowen
authors.initials: H
authors.lastname: Xiao
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Liu
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation; D011485:Protein Binding; D055550:Protein Stability; D034622:RNA Interference; D059505:Telomere Homeostasis; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C471644:BTRC protein, human; D044783:F-Box Proteins; D035321:Telomeric Repeat Binding Protein 1; D044844:beta-Transducin Repeat-Containing Proteins; D049452:Green Fluorescent Proteins