Post-translational modification of cyclin A1 is associated with staurosporine and TNFα induced apoptosis in leukemic cells

Ekberg, Jenny and Persson, Jenny Liao (2009) Post-translational modification of cyclin A1 is associated with staurosporine and TNFα induced apoptosis in leukemic cells. Molecular and Cellular Biochemistry, 320 1-2: 115-124. doi:10.1007/s11010-008-9913-3


Author Ekberg, Jenny
Persson, Jenny Liao
Title Post-translational modification of cyclin A1 is associated with staurosporine and TNFα induced apoptosis in leukemic cells
Journal name Molecular and Cellular Biochemistry   Check publisher's open access policy
ISSN 0300-8177
1573-4919
Publication date 2009-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1007/s11010-008-9913-3
Open Access Status
Volume 320
Issue 1-2
Start page 115
End page 124
Total pages 9
Editor Naranjan S Dhalla
Place of publication Secaucus, NJ, U.S.A.
Publisher Springer New York
Language eng
Subject C1
Abstract Understanding of molecular mechanisms underlying the effects of cell cycle proteins in response to the chemotherapeutic agents is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to chemotherapeutic agents. Staurosporine and tumor necrosis factor alpha (TNFα) are the therapeutic agents that inhibit tumor cell growth by inducing cell death. Staurosporine induces apoptosis through the intrinsic pathway, while TNFα trigger the cell death via the extrinsic apoptotic pathway. We have previously demonstrated that the cell cycle regulatory protein, cyclin A1 played an important role in the development of acute myeloid leukemia (AML), and cyclin A1 expression correlated with disease characteristics and patient outcome in leukemia. However, it remains unknown how cyclin A1 expression is regulated in leukemic cells treated with the therapeutic agents. Here, we demonstrate that cyclin A1 protein is regulated by proteasome-mediated ubiquitination and degradation in untreated U-937 cells. Interestingly, ubiquitination- and proteasomal-mediated degradation of cyclin A1 is prevented in cells treated with staurosporine or TNFα. Induction of apoptosis in U-937 cells by staurosporine or TNFα resulted in an increase in cyclin A1 protein expression, which correlated well with cyclin A1 protein modification and the activation of caspase-3. Blocking caspases activity by Z-VAD-FMK had no effect on the increased cyclin A1 expression, suggesting that cyclin A1 might be regulated by caspase-3 independent pathways. We further propose that CDC25C may be associated with cyclin A1 protein modification in response to staurosporine or TNFα treatment. Our results suggest that cyclin A1 protein is stabilized via post-transcriptional modification in response to apoptosis induced by staurosporine or TNFα.
Keyword Cyclin A1
Post-translational regulation
Apoptosis
Staurosporine
TNFα
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Published online: 12 September 2008

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
ERA 2012 Admin Only
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 20 Apr 2009, 13:43:57 EST by Timothy Hazelton on behalf of School of Biomedical Sciences