Expression and function of prostate-apoptosis-response-gene-4 in lymphatic cells.

Boehrer, Simone, Chow, Kai U., Ruthardt, Martin ORCID: https://orcid.org/0000-0003-1021-3811, Hoelzer, Dieter, Mitrou, Paris S. and Weidmann, Eckhart 2009. Expression and function of prostate-apoptosis-response-gene-4 in lymphatic cells. Leukemia & Lymphoma 43 (9) , pp. 1737-1741. 10.1080/1042819021000006510

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Abstract

Inhibition of apoptosis contributes to the pathogenesis of lymphatic malignancies. In particular, the elevated expression of Bcl-2 is considered to be a marker of poor prognosis, since increased levels of Bcl-2 confer longevity as well as chemoresistance. After demonstrating an inverse expressional pattern of Bcl-2 and prostate-apoptosis-response-4 (Par-4) in ex vivo cells of patients suffering from acute lymphatic leukemia (ALL) as well as a deregulated expression of Par-4 in acute and chronic lymphatic neoplasias, the molecular mechanisms underlying these results were investigated. Thus, it was demonstrated that in neoplastic lymphatic cells Par-4 exerts a proapoptotic role augmenting chemosensitivity by down-regulating Bcl-2, promoting disruption of mitochondrial membrane potential and enforcing caspase-activation. Moreover, Par-4 enables cells to circumvent inhibition of the central executioner caspase-3 by alternative activation of caspases following a decrease in expression levels of inhibitors of apoptosis proteins (IAP).

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Taylor and Francis Group
ISSN:	1042-8194
Last Modified:	29 Feb 2024 14:45
URI:	https://orca.cardiff.ac.uk/id/eprint/166052

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