Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation
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 cla...
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Published in | International journal of molecular medicine Vol. 18; no. 3; pp. 425 - 432 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Greece
D.A. Spandidos
01.09.2006
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1107-3756 1791-244X |
DOI: | 10.3892/ijmm.18.3.425 |