| The ubiquitin-proteasome pathway plays essential roles in ATRA-induced leukemia cells G0/G1 phase arrest and transition into granulocytic differentiation. | |
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MedLine Citation:
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PMID: 20935519 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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All-trans retinoic acid (ATRA) has been successfully used in differentiation therapy for acute promyelocytic leukemia (APL) in the clinic. ATRA-induced differentiation of leukemia cells is accompanied by a G0/G1 arrest, yet how ATRA couples cell cycle arrest to differentiation remains largely unknown. Here we observed that the ubiquitin-proteasome pathway (UPP) was activated upon ATRA treatment in the human acute myeloid leukemia cell lines, NB4 and HL-60, as represented by the accumulation of ubiquitinated proteins, the up-regulation of ubiquitin mRNA and increased 20S proteasome activity. Interestingly, we found that complete inhibition of proteasome activity suppressed ATRA-induced proliferation/differentiation (P/D) transition in both cell lines. Furthermore, we demonstrate that the exact protein contributing to this phenomenon is different in these two cell lines. Cyclin-dependent kinase 2 (CDK2) and Cyclin E were degraded by the UPP; they accumulated significantly after complete inhibition of the proteasome in ATRA-treated NB4 and HL-60 cells, respectively. These findings suggested that the UPP might be indispensable in the ATRA-induced G0/G1 arrest and differentiation of leukemia cells. The exact protein degraded by the UPP to promote the myeloid maturation program set in motion by the retinoid may be cell type dependent. |
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Authors:
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Yanfen Fang; Xinglu Zhou; Meihua Lin; Hui Jing; Like Zhong; Meidan Ying; Peihua Luo; Bo Yang; Qiaojun He |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-12-01 |
Journal Detail:
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Title: Cancer biology & therapy Volume: 10 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2011-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1157-67 Citation Subset: IM |
Affiliation:
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Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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