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RB and Lamins in Cell Cycle Regulation and Aging

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Cancer Biology and the Nuclear Envelope

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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

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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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  1. The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA

    Brian K. Kennedy Ph.D. & Juniper K. Pennypacker

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  1. Brian K. Kennedy Ph.D.
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  2. Juniper K. Pennypacker
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Correspondence to Brian K. Kennedy Ph.D. .

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  1. University of Edinburgh Wellcome Trust Centre for Cell Biology, Edinburgh, United Kingdom

    Eric C. Schirmer

  2. University of Edinburgh Wellcome Trust Centre for Cell Biology, Edinburgh, United Kingdom

    Jose I. de las Heras

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© 2014 Springer Science+Business Media New York

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Kennedy, B.K., Pennypacker, J.K. (2014). RB and Lamins in Cell Cycle Regulation and Aging. In: Schirmer, E., de las Heras, J. (eds) Cancer Biology and the Nuclear Envelope. Advances in Experimental Medicine and Biology, vol 773. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8032-8_6

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