Inflammation-associated cell cycle-independent block of apoptosis by survivin in terminally differentiated neutrophils.

Altznauer, Frank; Martinelli, Sibylla; Yousefi, Shida; Thürig, Christine; Schmid, Inès; Conway, Edward M; Schöni, Martin H; Vogt, Peter; Mueller, Christoph; Fey, Martin F; Zangemeister-Wittke, Uwe; Simon, Hans-Uwe (2004). Inflammation-associated cell cycle-independent block of apoptosis by survivin in terminally differentiated neutrophils. The Journal of experimental medicine, 199(10), pp. 1343-1354. Rockefeller Univ. Press 10.1084/jem.20032033

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Survivin has received great attention due to its expression in many human tumors and its potential as a therapeutic target in cancer. Survivin expression has been described to be cell cycle-dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells. In agreement with this current view, we found that survivin expression was high in immature neutrophils, which proliferate during differentiation. In contrast with immature cells, mature neutrophils contained only little or no survivin protein. Strikingly, these cells reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF) or granulocyte CSF stimulation in vitro and under inflammatory conditions in vivo. Moreover, survivin-deficient mature neutrophils were unable to increase their lifespan after survival factor exposure. Together, our findings demonstrate the following: (a) overexpression of survivin occurs in primary, even terminally differentiated cells and is not restricted to proliferating cells; and (b) survivin acts as an inhibitor of apoptosis protein in a cell cycle-independent manner. Therefore, survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells. These data provide new insights into the regulation and function of survivin and have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases and cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Yousefi, Shida; Schöni, Martin Heinrich; Müller, Christoph; Fey, Martin and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1540-9538

Publisher:

Rockefeller Univ. Press

Language:

English

Submitter:

Christoph Müller

Date Deposited:

27 Sep 2022 06:58

Last Modified:

27 Sep 2022 07:06

Publisher DOI:

10.1084/jem.20032033

PubMed ID:

15148334

BORIS DOI:

10.48350/173175

URI:

https://boris.unibe.ch/id/eprint/173175

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