p27KIP1 is down-regulated by two different mechanisms in human lymphoid cells undergoing apoptosis

Frost, V and Sinclair, AJ (2000) p27KIP1 is down-regulated by two different mechanisms in human lymphoid cells undergoing apoptosis. Oncogene, 19 (27). pp. 3115-3120. ISSN 0950-9232

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Abstract

The cyclin-dependent kinase inhibitor p27KIP1 is a crucial component of the mammalian restriction point, and as such is subject to multiple regulatory mechanisms. It has recently been shown that the abundance of p27KIP1 is also regulated during apoptosis; p27KIP1 is cleaved by a Z-VAD-fmk-sensitive caspase during apoptosis induced by growth factor deprivation in endothelial cells, and also following exposure of myeloid leukaemia cells to etoposide. Here, we investigate p27KIP1 regulation in B- and T-lymphoid cells undergoing apoptosis. We observe that p27KIP1 is down-regulated following exposure to a variety of apoptotic stimuli including an agonistic anti-Fas antibody, cycloheximide and etoposide. Further investigation revealed the existence of two different routes of p27KIP1 regulation in lymphoid cells undergoing apoptosis. The first pathway is utilized by lymphoid cells stimulated through Fas, is abrogated in a caspase-8-deficient T-cell line, and is blocked by the caspase inhibitors Z-VAD-fmk and Boc-D-fmk. In contrast, the loss of p27KIP1 in cells exposed to cycloheximide and etoposide occurs in the absence of caspase-8 or any Z-VAD-fmk- or Boc-D-fmk-sensitive caspase activities. Thus the down-regulation of p27KIP1 is a common occurrence in lymphoid cells undergoing apoptosis but, depending on the apoptotic trigger, this can be affected by two different mechanisms.

Item Type: Article
Additional Information: The top journal concerning the molecular biology of cancer
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Alison Sinclair
Date Deposited: 06 Feb 2012 19:30
Last Modified: 30 Mar 2012 15:23
URI: http://sro.sussex.ac.uk/id/eprint/20947
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