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Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9677-82. Epub 2004 Jun 21.

A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation.

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  • 1Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.

Abstract

The retinoblastoma protein (pRB) is a critical regulator of cell proliferation and differentiation and an important tumor suppressor. In the G(1) phase of the cell cycle, pRB localizes to perinucleolar sites associated with lamin A/C intranuclear foci. Here, we examine pRB function in cells lacking lamin A/C, finding that pRB levels are dramatically decreased and that the remaining pRB is mislocalized. We demonstrate that A-type lamins protect pRB from proteasomal degradation. Both pRB levels and localization are restored upon reintroduction of lamin A. Lmna(-/-) cells resemble Rb(-/-) cells, exhibiting altered cell-cycle properties and reduced capacity to undergo cell-cycle arrest in response to DNA damage. These findings establish a functional link between a core nuclear structural component and an important cell-cycle regulator. They further raise the possibility that altered pRB function may be a contributing factor in dystrophic syndromes arising from LMNA mutation.

PMID:
15210943
[PubMed - indexed for MEDLINE]
PMCID:
PMC470734
Free PMC Article

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