Regulation of p27KIP1 in Epstein–Barr virus-immortalized lymphoblastoid cell lines involves non-apoptotic caspase cleavage

Frost, Victoria, Delikat, Sylvie, Al-Mehairi, Salama and Sinclair, Alison J. (2001) Regulation of p27KIP1 in Epstein–Barr virus-immortalized lymphoblastoid cell lines involves non-apoptotic caspase cleavage. Journal of General Virology, 82 (12). pp. 3057-3066. ISSN 0022-1317

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Abstract

The cyclin-dependent kinase inhibitor p27(KIP1) plays a key role in controlling cell proliferation. Here we show that p27(KIP1) is commonly down-regulated in B-cells immortalized by Epstein-Barr virus (EBV) (lymphoblastoid cell lines, LCLs). The significance of this event for the immortal phenotype of LCLs is implied by a requirement for active cdk2-containing complexes for continued proliferation, and by the ability of the residual p27 KIN to associate with cdk2. The mechanism of p27(KIP1) attenuation is post-translational, but inhibitor studies reveal that the mechanism does not rely heavily on the proteasome. Instead we find that LCLs contain an activity that cleaves a caspase recognition site present in p27(KIP1) (DPSD139). The activity is not associated with apoptosis and closely resembles a proliferation-associated caspase activity we previously described in the p27(KIP1)-negative B-lymphoma-derived cell line BJAB. Importantly, proliferating LCLs contain a p27(KIP1) product that is consistent with cleavage at this site. Inhibition of caspase(s) in vivo modulates p27(KIP1) expression and strongly inhibits proliferation of IB4 cells. This inhibitor profile is identical to that displayed by the DPSD-directed caspase present in BJAB cells, suggesting that the caspase may fulfil a general role in controlling p27(KIP1) expression in immortal lymphoid cell lines. Thus, apoptosis-independent cleavage appears to contribute to the maintenance of the low basal levels of p27(KIP1) in B-cells immortalized by EBV.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Alison Sinclair
Date Deposited: 06 Feb 2012 19:53
Last Modified: 01 May 2012 15:05
URI: http://sro.sussex.ac.uk/id/eprint/22764
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