Loss of tumor suppressor RPL5/RPL11 does not induce cell cycle arrest but impedes proliferation due to reduced ribosome content and translation capacity

Teng Teng, Carol A. Mercer, Philip Hexley, George Thomas, Stefano Fumagalli

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Humans have evolved elaborate mechanisms to activate p53 in response to insults that lead to cancer, including the binding and inhibition of Hdm2 by the 60S ribosomal proteins (RPs) RPL5 and RPL11. This same mechanism appears to be activated upon impaired ribosome biogenesis, a risk factor for cancer initiation. As loss of RPL5/RPL11 abrogates ribosome biogenesis and protein synthesis to the same extent as loss of other essential 60S RPs, we reasoned the loss of RPL5 and RPL11 would induce a p53-independent cell cycle checkpoint. Unexpectedly, we found that their depletion in primary human lung fibroblasts failed to induce cell cycle arrest but strongly suppressed cell cycle progression. We show that the effects on cell cycle progression stemmed from reduced ribosome content and translational capacity, which suppressed the accumulation of cyclins at the translational level. Thus, unlike other tumor suppressors, RPL5/RPL11 play an essential role in normal cell proliferation, a function cells have evolved to rely on in lieu of a cell cycle checkpoint.

Original languageEnglish (US)
Pages (from-to)4660-4671
Number of pages12
JournalMolecular and cellular biology
Volume33
Issue number23
DOIs
StatePublished - Dec 2013

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Cell Cycle Checkpoints
Ribosomes
Ribosomal Proteins
Cell Cycle
Neoplasms
Cyclins
Fibroblasts
Cell Proliferation
Lung
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Loss of tumor suppressor RPL5/RPL11 does not induce cell cycle arrest but impedes proliferation due to reduced ribosome content and translation capacity. / Teng, Teng; Mercer, Carol A.; Hexley, Philip; Thomas, George; Fumagalli, Stefano.

In: Molecular and cellular biology, Vol. 33, No. 23, 12.2013, p. 4660-4671.

Research output: Contribution to journalArticle

Teng, Teng ; Mercer, Carol A. ; Hexley, Philip ; Thomas, George ; Fumagalli, Stefano. / Loss of tumor suppressor RPL5/RPL11 does not induce cell cycle arrest but impedes proliferation due to reduced ribosome content and translation capacity. In: Molecular and cellular biology. 2013 ; Vol. 33, No. 23. pp. 4660-4671.
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