title: Interaction between RB protein and NuMA is required for proper alignment of spindle microtubules.
abstract: Retinoblastoma protein (pRB) controls cell cycle progression and cell cycle exit through interactions with cellular proteins. Many pRB-binding proteins, which function in gene transcription or modulation of chromatin structure, harbor LXCXE motifs in their binding domain for pRB. In this study, we found that nuclear mitotic apparatus protein (NuMA), a mitotic spindle organizer, interacts with pRB through LSCEE sequences located in its C-terminal region. siRNA-mediated down-regulation of pRB caused aberrant distribution of NuMA and alignment of spindle microtubules in mitotic cells. Abnormal organization of spindle microtubules was also accompanied by misalignment of an over-expressed NuMA mutant (mut-NuMA) with a defect in pRB binding caused by an LSGEK mutation. The mut-NuMA-over-expressing cells showed lower potency for survival than wild-type NuMA (wt-NuMA)-over-expressing cells during 2 weeks of culture. Interestingly, knockdown of pRB reduced the population of wt-NuMA-over-expressing cells to the same level as mut-NuMA cells after 2 weeks. Taken together, pRB may have a novel function in regulating the mitotic function of NuMA and spindle organization, which are required for proper cell cycle progression.
authors.affiliation: Research Equipment Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan; Cancer Science Institute of Singapore (CSI-Singapore), National University of Singapore, Centre for Translational Medicine, 14 Medical Drive, #12-01, 117599, Singapore.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Uchida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hattori
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Takahashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Taya
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D006801:Humans; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D008938:Mitosis; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein