GNL3L stabilizes the TRF1 complex and promotes mitotic transition.
Telomeric repeat binding factor 1 (TRF1) is a component of the multiprotein complex "shelterin," which organizes the telomere into a high-order structure. TRF1 knockout embryos suffer from severe growth defects without apparent telomere dysfunction, suggesting an obligatory role for TRF1 in cell cycle control. To date, the mechanism regulating the mitotic increase in TRF1 protein expression and its function in mitosis remains unclear. Here, we identify guanine nucleotide-binding protein-like 3 (GNL3L), a GTP-binding protein most similar to nucleostemin, as a novel TRF1-interacting protein in vivo. GNL3L binds TRF1 in the nucleoplasm and is capable of promoting the homodimerization and telomeric association of TRF1, preventing promyelocytic leukemia body recruitment of telomere-bound TRF1, and stabilizing TRF1 protein by inhibiting its ubiquitylation and binding to FBX4, an E3 ubiquitin ligase for TRF1. Most importantly, the TRF1 protein-stabilizing activity of GNL3L mediates the mitotic increase of TRF1 protein and promotes the metaphase-to-anaphase transition. This work reveals novel aspects of TRF1 modulation by GNL3L.
Zhu
Qubo
Q
Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA.
Meng
Lingjun
L
Hsu
Joseph K
JK
Lin
Tao
T
Teishima
Jun
J
Tsai
Robert Y L
RY
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D019281:Dimerization; D044783:F-Box Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054875:Ubiquitination
D044783:F-Box Proteins; C515213:Fbx4 protein, mouse; C524643:GNL3L protein, mouse; D009687:Nuclear Proteins; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; C499083:Tinf2 protein, mouse; D019098:Telomerase; C509187:Tert protein, mouse; D019204:GTP-Binding Proteins