title: CYLD coordinates with EB1 to regulate microtubule dynamics and cell migration.
abstract: Cylindromatosis (CYLD), a deubiquitinase involved in inflammation and tumorigenesis via the modulation of cell signaling, has recently been identified as a critical regulator of microtubule dynamics. CYLD has also been shown to stimulate cell migration and thereby contribute to normal physiological processes. However, it remains elusive how the regulation of microtubule dynamic properties by CYLD is connected to its role in mediating cell migration. In this study, we performed yeast 2-hybrid screening with CYLD as bait and identified 7 CYLD-interacting proteins, including end-binding protein 1 (EB1). The CYLD-EB1 interaction was confirmed both in cells and in vitro, and these 2 proteins colocalized at the plus ends of microtubules. Interestingly, the association of CYLD with EB1 was significantly increased upon the stimulation of cell migration. CYLD coordinated with EB1 to orchestrate tail retraction, centrosome reorientation, and leading-edge microtubule stabilization in migratory cells. In addition, CYLD acted in concert with EB1 to regulate microtubule assembly in vitro, microtubule nucleation at the centrosome, and microtubule growth at the cell periphery. These data provide mechanistic insights into the actions of CYLD in the regulation of microtubule dynamics and cell migration. These findings also support the notion that coordinated actions of microtubule-binding proteins are critical for microtubule-mediated cellular events.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences; Nankai University; Tianjin, China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences; Nankai University; Tianjin, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences; Nankai University; Tianjin, China.
authors.forename: Yunfan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics; School of Basic Medical Sciences; Tianjin Medical University; Tianjin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences; Nankai University; Tianjin, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Suo
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences; Nankai University; Tianjin, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences; Nankai University; Tianjin, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Shui
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences; Nankai University; Tianjin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics; School of Basic Medical Sciences; Tianjin Medical University; Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D018385:Centrosome / Q000502:physiology; D000074749:Deubiquitinating Enzyme CYLD; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: CYLD; EB1; cell migration; centrosome; microtubule; yeast-two hybrid