Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation

  • Authors:
    • Tokuhiro Chano
    • Masashi Saji
    • Hirokazu Inoue
    • Kahori Minami
    • Toshiyuki Kobayashi
    • Okio Hino
    • Hidetoshi Okabe
  • View Affiliations

  • Published online on: September 1, 2006     https://doi.org/10.3892/ijmm.18.3.425
  • Pages: 425-432
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Abstract

RB1-inducible coiled-coil 1 (RB1CC1) is a novel tumor suppressor implicated in the regulation of RB1 expression. It is abundant in post-mitotic neuromuscular cells, which are matured and enlarged, but scarce in smaller leukocytes, indicating an association between RB1CC1 status and cell size. To clarify whether RB1CC1 is involved in cell size control, we investigated the contribution of RB1CC1 to the TSC-mTOR pathway, which plays an important role in the control through translational regulation. RNAi-mediated knockdown of RB1CC1 reduced the activation of mTOR and S6K as well as the size of HEK293 and C2C12 cells. Such knockdown also suppressed RB1 expression and the population of G1-phase cells. Exogenous expression of RB1CC1 maintained S6K activity and cell size, and decreased TSC1/hamartin contents under nutritionally starved conditions, which usually inhibit the mTOR-S6K pathway. Furthermore, RB1CC1 interfered with and degraded TSC1 through the ubiquitin-proteasomal pathway. A lentiviral RNAi for RB1CC1 reduced the size of mouse leg muscles. These findings suggest that RB1CC1 is required to maintain both RB1 expression and mTOR activity. The activity of mTOR was supported by RB1CC1 through TSC1 degradation. RB1CC1 preserved cell size without cell cycle progression especially in neuromuscular tissues, and the abundance contributed to the non-proliferating enlarged cell phenotype.

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September 2006
Volume 18 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chano T, Saji M, Inoue H, Minami K, Kobayashi T, Hino O and Okabe H: Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation. Int J Mol Med 18: 425-432, 2006
APA
Chano, T., Saji, M., Inoue, H., Minami, K., Kobayashi, T., Hino, O., & Okabe, H. (2006). Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation. International Journal of Molecular Medicine, 18, 425-432. https://doi.org/10.3892/ijmm.18.3.425
MLA
Chano, T., Saji, M., Inoue, H., Minami, K., Kobayashi, T., Hino, O., Okabe, H."Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation". International Journal of Molecular Medicine 18.3 (2006): 425-432.
Chicago
Chano, T., Saji, M., Inoue, H., Minami, K., Kobayashi, T., Hino, O., Okabe, H."Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation". International Journal of Molecular Medicine 18, no. 3 (2006): 425-432. https://doi.org/10.3892/ijmm.18.3.425