title: A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle.
abstract: Pin2/TRF1 was independently identified as a telomeric DNA binding protein (TRF1) [1] and as a protein (Pin2) that can bind the mitotic kinase NIMA and suppress its ability to induce mitotic catastrophe [2, 3]. Pin2/TRF1 has been shown to bind telomeric DNA as a dimer [3-7] and to negatively regulate telomere length [8-11]. Interestingly, Pin2/TRF1 levels are regulated during the cell cycle, being increased in late G2 and mitosis and degraded as cells exit from mitosis [3]. Furthermore, overexpression of Pin2/TRF1 induces mitotic entry and then apoptosis [12]. This Pin2/TRF1 activity can be significantly potentiated by the microtubule-disrupting agent nocodazole [12] but is suppressed by phosphorylation of Pin2/TRF1 by ATM; this negative regulation is important for preventing apoptosis upon DNA damage [13]. These results suggest a role for Pin2/TRF1 in mitosis. However, nothing is known about how Pin2/TRF1 is involved in mitotic progression. Here, we describe a surprising physical interaction between Pin2/TRF1 and microtubules in a cell cycle-specific manner. Both expressed and endogenous Pin2/TRF1 proteins were localized to the mitotic spindle during mitosis. Furthermore, Pin2/TRF1 directly bound microtubules via its C-terminal domain. Moreover, Pin2/TRF1 also promoted microtubule polymerization in vitro. These results demonstrate for the first time a specific interaction between Pin2/TRF1 and microtubules in a mitosis-specific manner, and they suggest a new role for Pin2/TRF1 in modulating the function of microtubules during mitosis.
authors.affiliation: Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 02215, Boston, MA, USA
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: X Z
authors.initials: XZ
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Kishi
authors.forename: I
authors.initials: I
authors.lastname: Kosugi
authors.forename: Y
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: K P
authors.initials: KP
authors.lastname: Lu
mesh_terms: D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D011108:Polymers; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D011108:Polymers; D011993:Recombinant Fusion Proteins; D035321:Telomeric Repeat Binding Protein 1