50
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Current topics of functional links between primary cilia and cell cycle

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Primary cilia, microtubule-based sensory structures, orchestrate various critical signals during development and tissue homeostasis. In view of the rising interest into the reciprocal link between ciliogenesis and cell cycle, we discuss here several recent advances to understand the molecular link between the individual step of ciliogenesis and cell cycle control. At the onset of ciliogenesis (the transition from centrosome to basal body), distal appendage proteins have been established as components indispensable for the docking of vesicles at the mother centriole. In the initial step of axonemal extension, CP110, Ofd1, and trichoplein, key negative regulators of ciliogenesis, are found to be removed by a kinase-dependent mechanism, autophagy, and ubiquitin–proteasome system, respectively. Of note, their disposal functions as a restriction point to decide that the axonemal nucleation and extension begin. In the elongation step, Nde1, a negative regulator of ciliary length, is revealed to be ubiquitylated and degraded by CDK5-SCF Fbw7 in a cell cycle-dependent manner. With regard to ciliary length control, it has been uncovered in flagellar shortening of Chlamydomonas that cilia itself transmit a ciliary length signal to cytoplasm. At the ciliary resorption step upon cell cycle re-entry, cilia are found to be disassembled not only by Aurora A-HDAC6 pathway but also by Nek2-Kif24 and Plk1-Kif2A pathways through their microtubule-depolymerizing activity. On the other hand, it is becoming evident that the presence of primary cilia itself functions as a structural checkpoint for cell cycle re-entry. These data suggest that ciliogenesis and cell cycle intimately link each other, and further elucidation of these mechanisms will contribute to understanding the pathology of cilia-related disease including cancer and discovering targets of therapeutic interventions.

          Related collections

          Most cited references104

          • Record: found
          • Abstract: not found
          • Article: not found

          CDK inhibitors: positive and negative regulators of G1-phase progression.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Ubiquitin ligases: cell-cycle control and cancer.

            A driving force of the cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin ligases, the SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C), are responsible for the specific ubiquitylation of many of these regulators. Deregulation of the proteolytic system might result in uncontrolled proliferation, genomic instability and cancer. Cumulative clinical evidence shows alterations in the ubiquitylation of cell-cycle regulators in the aetiology of many human malignancies. A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Centrioles, centrosomes, and cilia in health and disease.

              Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis of these organelles, and we emphasize their connection to human disease. Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in centrosomal proteins have recently been genetically linked to microcephaly and dwarfism. Finally, structural or functional centriole aberrations contribute to ciliopathies, a variety of complex diseases that stem from the absence or dysfunction of cilia.
                Bookmark

                Author and article information

                Contributors
                iizawa@aichi-cc.jp
                hgoto@aichi-cc.jp
                kkasahara@aichi-cc.jp
                minagaki@aichi-cc.jp
                Journal
                Cilia
                Cilia
                Cilia
                BioMed Central (London )
                2046-2530
                29 December 2015
                29 December 2015
                2015
                : 4
                : 12
                Affiliations
                [ ]Division of Biochemistry, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681 Japan
                [ ]Department of Cellular Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550 Japan
                [ ]Department of Oncology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603 Japan
                Article
                21
                10.1186/s13630-015-0021-1
                4696186
                26719793
                1d4eeea7-8dda-41ca-85b3-99af24382331
                © Izawa et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 September 2015
                : 10 December 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001700, Ministry of Education, Culture, Sports, Science, and Technology (JP);
                Award ID: 24113005
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100008732, Uehara Memorial Foundation;
                Funded by: FundRef http://dx.doi.org/10.13039/100007449, Takeda Science Foundation;
                Funded by: Princess Takamatsu Cancer Research Fund
                Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award ID: 25460089
                Award ID: 15K08324
                Award ID: 15H02398
                Award ID: 26670650
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2015

                Cell biology
                primary cilia,cell cycle,ciliogenesis,ubiquitin–proteasome system,cancer
                Cell biology
                primary cilia, cell cycle, ciliogenesis, ubiquitin–proteasome system, cancer

                Comments

                Comment on this article