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A novel specific cleavage of IκBα protein in acute myeloid leukemia cells involves protease PR3.
- Source :
-
Experimental cell research [Exp Cell Res] 2019 Sep 01; Vol. 382 (1), pp. 111441. Date of Electronic Publication: 2019 May 22. - Publication Year :
- 2019
-
Abstract
- IκBα protein plays an important role in NFκB signaling pathway regulation. The dysfunction of IκBα is tightly related to various diseases, including cancers. However, the molecular mechanisms by which IκBα loses its normal functions are diverse and complex. Here, we reported a novel cleavage of IκBα protein occurred in AML cells. Compared with the full-length IκBα protein, the truncated IκBα fragment exhibited a dramatically weak binding ability to NFκB complex and showed a significant decreased inhibition on NFκB transactivation. Knockdown of PR3, a serine protease mainly expressed in myeloid cells, could inhibit such IκBα cleavage and enhance the sensitivities of AML cells to the differentiation inducers. In addition, we showed that the level of PR3 mRNA was relatively higher in newly diagnosed AML patients than in those patients with complete remission, suggesting that PR3 expression and its involvement in IκBα cleavage might be closely associated with AML. Our studies revealed for the first time a PR3-involved IκBα cleavage in AML cells, providing some new evidences for further understanding the mechanisms underlying the deregulation of NFκB pathway in AML. Finally, we also suggested a potential clinical application value of PR3 protein in the treatment and prognosis surveillance for leukemia.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Gene Expression Regulation, Leukemic
Gene Knockdown Techniques
Humans
Leukemia, Myeloid, Acute genetics
Myeloblastin antagonists & inhibitors
Myeloblastin genetics
NF-kappa B metabolism
Protease Inhibitors pharmacology
RNA Interference
RNA, Messenger biosynthesis
RNA, Messenger genetics
RNA, Neoplasm biosynthesis
RNA, Neoplasm genetics
RNA, Small Interfering genetics
RNA, Small Interfering pharmacology
Recombinant Proteins metabolism
Leukemia, Myeloid, Acute metabolism
Myeloblastin metabolism
NF-KappaB Inhibitor alpha metabolism
Neoplasm Proteins metabolism
Protein Processing, Post-Translational
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 382
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 31125555
- Full Text :
- https://doi.org/10.1016/j.yexcr.2019.05.022