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Review
. 2013 Jul;183(1):3-9.
doi: 10.1016/j.ajpath.2013.03.001.

New Roles of Cyclin D1

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Free PMC article
Review

New Roles of Cyclin D1

Richard G Pestell. Am J Pathol. .
Free PMC article

Abstract

Cyclins encode regulatory subunits of holoenzymes that phosphorylate a variety of cellular substrates. Although the classic role of cyclins in cell cycle progression and tumorigenesis has been well characterized, new functions have been identified, including the induction of cellular migration and invasion, enhancement of angiogenesis, inhibition of mitochondrial metabolism, regulation of transcription factor signaling via a DNA-bound form, the induction of chromosomal instability, enhancement of DNA damage sensing and DNA damage repair, and feedback governing expression of the noncoding genome. This review describes the mechanisms of these new functions of cyclin D1.

Figures

Figure 1
Figure 1
Cyclin D1 inhibits mitochondrial biogenesis. A: Schematic representation of the mechanism by which cyclin D1 inhibits mitochondrial function. Cyclin D1–dependent kinase phosphorylates and inhibits NRF-1 and, thereby, mitochondrial transcription factor A and mitochondrial activity. B: Cyclin D1 deficiency enhances mitochondrial size and function. Transmission electron microscopic images of hepatocytes from liver tissue of cyclin D1+/+ (red box, enlarged area) and cyclin D1−/− (yellow box, enlarged area) show increased mitochondria size in cyclin D1−/−. Catalase-positive peroxisomes (dark spherical structures) are evident. Original magnification, ×5000 (right column).
Figure 2
Figure 2
Schematic representation of cyclin D1 interactions. Schematic representation of functions shown to involve CDK binding with other interactions shown as either CDK independent or unknown.
Figure 3
Figure 3
Hypothetical functional interaction between cyclin D1 as a kinase complex, which phosphorylates pRb and NRF1, and the DNA-bound form, which binds promoters of genes regulating CIN, to promote oncogenesis.

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