RB and Lamins in Cell Cycle Regulation and Aging

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 773)

Abstract

While speculation has centered on a role for nuclear lamins in tumor progression for many years, most of the diseases that have been linked to lamin mutation are dystrophic in nature, often limiting the proliferation potential of affected cells in vivo and in vitro. Nevertheless, these lamin mutations, particularly in the LMNA gene that encodes A-type lamins, have provided an interesting tool set to understand functions of nuclear intermediate filament proteins in cell cycle progress and various means of exit, including quiescence, senescence, and differentiation down various lineages. The picture that has emerged is complex with lamins controlling the activity of key cell cycle factors such as the retinoblastoma protein (RB) and interacting with several important signal transduction pathways. Here we describe the current state of knowledge and speculate that lamins may be intimately involved in the regulation of cell proliferation, acting at the interface between cancer and aging.

Keywords

A-type lamins B-type lamins Retinoblastoma protein LMNA gene Lamins Aging Progerin Senescence Cancer Cell cycle progression Telomeres p53 

Abbreviations

ATR

Ataxia telangiectasia and Rad3-related protein

ADLD

Autosomal dominant leukodystrophy

CDK

Cyclin-dependent kinase

DCM1A

Dilated cardiomyopathy type 1A

ERK

Extracellular signal-regulated kinases

HGPS

Hutchinson–Gilford Progeria syndrome

LAP2α

Lamina-associated polypeptide 2α

MDM2

Mouse double minute 2 homolog

ROS

Reactive oxygen species

RB

Retinoblastoma protein

SASP

Senescence-associated secretory phenotype

SIRT1

Silent mating-type information regulation 2 homolog 1

VHL

von Hippel–Lindau gene

Notes

Acknowledgements

Lamin-related research in the lab of B.K.K. is supported by a grant from the National Institute of Aging (R01 AG024287).

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.The Buck Institute for Research on AgingNovatoUSA

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