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Sci. Signal., 25 March 2008
Vol. 1, Issue 12, p. pt1
[DOI: 10.1126/stke.112pt1]

PRESENTATIONS

Matrix Metalloproteinase-7 and the 20S Proteasome Contribute to Cellular Senescence

Catharina Bertram{dagger} and Ralf Hass*

Department of Gynecology, Biochemistry and Tumor Biology Unit, Medical School, Hannover, Germany.
{dagger}Presenter.

A presentation from the 11th Joint Meeting of the Signal Transduction Society (STS), Signal Transduction: Receptors, Mediators and Genes, Weimar, Germany, 1 to 3 November 2007.

Abstract: A detailed understanding of aging and senescence is limited by the complex interplay of the effects of extracellular and environmental stimuli on cellular metabolic, mutational, and epigenetic phenomena. For example, STASIS (stress or aberrant signaling–induced senescence) is affected by the exposure to free radicals and conditions that cause an increased cellular production of reactive oxygen species (ROS) during normal life span. In addition, progressive telomere erosion and telomeric dysfunction contribute to a cellular feature termed replicative or cellular senescence. To focus on distinct cellular pathways that contribute to these different forms of senescence, we investigated the reversible differentiation and aging process of the human U937 leukemia cell line. This was compared to cellular senescence that occurred in normal primary human mammary epithelial cells (HMECs). These two cell systems revealed an important role of the proteolytic activity of the 20S proteasome and its activation by the nuclear protein poly(ADP-ribose) polymerase–1 (PARP-1) during "retrodifferentiation" and rejuvenation of the leukemic cells. Moreover, reduced extracellular proteolytic activity of certain matrix metalloproteinases—for example, MMP-7—is associated with accelerated aging and senescence in normal HMECs.

*Corresponding author. Address: Department of Gynecology, Biochemistry and Tumor Biology Unit, Medical School, Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. E-mail, hass.ralf{at}mh-hannover.de

Citation: C. Bertram, R. Hass, Matrix Metalloproteinase-7 and the 20S Proteasome Contribute to Cellular Senescence. Sci. Signal. 1, pt1 (2008).

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