Isoform‐specific cleavage of 14‐3‐3 proteins in apoptotic JURL‐MK1 cells

Abstract

The proteins of 14-3-3 family are substantially involved in the regulation of many biological processes including the apoptosis. We studied the changes in the expression of five 14-3-3 isoforms (beta, gamma, epsilon, tau, and zeta) during the apoptosis of JURL-MK1 and K562 cells. The expression level of all these proteins markedly decreased in relation with the apoptosis progression and all isoforms underwent truncation, which probably corresponds to the removal of several C-terminal amino acids. The observed 14-3-3 modifications were partially blocked by caspase-3 inhibition. In addition to caspases, a non-caspase protease is likely to contribute to 14-3-3's cleavage in an isoform-specific manner. While 14-3-3 gamma seems to be cleaved mainly by caspase-3, the alternative mechanism is essentially involved in the case of 14-3-3 tau, and a combined effect was observed for the isoforms epsilon, beta, and zeta. We suggest that the processing of 14-3-3 proteins could form an integral part of the programmed cell death or at least of some apoptotic pathways.

Prostacyclin and PPARα Agonists Control Vascular Smooth Muscle Cell Apoptosis and Phenotypic Switch through Distinct 14-3-3 Isoforms

“…Z-DEVD-fmk at 20 µM prevented 14-3-3β but not 14-3-3θ depression by H 2 O 2 (Figure 2B). The result is consistent with a previous report that caspase 3 degrades 14-3-3β but not θ [19]. H 2 O 2 -induced 14-3-3β and θ reduction was reversed by pretreatment with Wy14,643 (Figure 2A).…”

Differential Proteomic Analysis of Human Erythroblasts Undergoing Apoptosis Induced by Epo-Withdrawal

“…Western blotting conducted on apoptotic cell lysates detected a proteolytic fragment of ∼37 kD for Hsp90 alpha (N-terminus) and of ∼50 kD (C-terminus) for Hsp90 beta (Figure 4) consistent with the sizes predicted for caspase cleavage. For 14-3-3 beta, gamma and epsilon, the molecular weight of the cleaved form was only marginally smaller than that of the full length proteins, mirroring what has already been described for caspase-mediated cleavage of 14-3-3 proteins [35].…”

DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach

“…This protein is downregulated during apoptosis of JURL-MK1 and K562 cells. 26 We also observed increased expression of cytokeratin 18 (a marker of cell death) and cytokeratin 19, and decreased expression of cytokeratin 8 after DAMTC treatment. Cytokeratins are important constituent of intermediate filaments and several investigators have shown an important role of these cytokeratins in signal transduction and apoptosis pathways.…”