title: Nucleolar modulation of TRF1: a dynamic way to regulate telomere and cell cycle by nucleostemin and GNL3L.
abstract: Chromosomal ends are protected by a high-order structure called telomere. Maintenance of correct telomere length and structure is critically important for the viability of both dividing and non-dividing cells. Notably, targeted deletion of a component of the multi-protein telomere-capping complex, TRF1 (telomeric repeat binding factor 1), causes lethality at embryonic day 5-6 without apparent telomere deficiency, raising the possibility that TRF1 may also moonlight outside the telomere. Further reinforcing the extra-telomeric tie of TRF1, two studies from our group have reported the findings that TRF1 can be bound and modulated by two nucleolar GTP-binding proteins, nucleostemin (NS) and guanine nucleotide binding protein-like 3-like (GNL3L), which exhibit apparently opposite effects on the protein degradation of TRF1. In particular, GNL3L is able to stabilize TRF1 protein during mitosis and promote the metaphase-to-anaphase transition. This manuscript extends the discussion on how this GNL3L-mediated TRF1 regulation creates a novel dynamic control on telomere and cell cycle, and extrapolates its evolutionary significance by contrasting the activities of NS and GNL3L.
authors.affiliation: Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX, USA. rtsai@ibt.tamhsc.edu
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Tsai
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002466:Cell Nucleolus; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C469949:GNL3 protein, human; C509155:GNL3L protein, human; D009687:Nuclear Proteins; D035321:Telomeric Repeat Binding Protein 1; D019204:GTP-Binding Proteins