| The leukocyte integrins are regulated by transcriptional and post-transcriptional mechanisms in a leukemic cell that overexpresses protein kinase C-zeta. | |
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MedLine Citation:
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PMID: 11713605 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Overexpression of protein kinase C-zeta (PKC-zeta) in the leukemic myeloid cell line U937 (U937-PKC-zeta cells), previously shown to induce leukemic cell differentiation, resulted in nearly complete downregulation of leukocyte integrins CD11a, CD11b, CD11d, and CD18, but not CD11c from the cell surface. The steady-state level of mRNAs for the downregulated leukocyte integrins was not detectable by Northern analysis. Nuclear run-on analysis revealed that transcription of all the leukocyte integrin genes except CD11c was reduced 70-90% as compared to control U937-Vector cells [U937 cells transfected with the empty vector pSV2M(2)6]. Transfection analysis of CD11-promoter-luciferase constructs confirmed that transcription of the leukocyte integrin genes was drastically downregulated in U937-PKC-zeta cells. The two c-jun binding sites in the CD11c promoter were essential for continued expression of CD11c in U937-PKC-zeta cells. Additionally, the 3' untranslated region (3' UTR) from CD11b, when fused to the luciferase gene, lead to the destabilization of this chimeric mRNA in U937-PKC-zeta cells. This indicates that downregulation of CD11b expression in U937-PKC-zeta cells is also the result of reduced stability of CD11b mRNA. Thus, overexpression of PKC-zeta in U937 cells leads not only to leukemic cell differentiation, but also to differential regulation of the leukocyte integrins. |
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Authors:
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J D Noti; B C Reinemann; A K Johnson |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: International journal of oncology Volume: 19 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2001 Dec |
Date Detail:
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Created Date: 2001-11-19 Completed Date: 2002-03-22 Revised Date: 2009-04-07 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 1311-8 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Biology, Guthrie Research Institute, Sayre, PA 18840, USA. jnoti@inet.guthrie.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3' Untranslated Regions Antigens, CD18 / genetics, metabolism* Blotting, Northern Flow Cytometry Gene Expression Regulation Humans Integrin alphaXbeta2 / genetics, metabolism* Leukocytes / enzymology* Luciferases / metabolism Lymphocyte Function-Associated Antigen-1 / genetics, metabolism* Macrophage-1 Antigen / genetics, metabolism* Promoter Regions, Genetic Protein Kinase C / metabolism* Proto-Oncogene Proteins c-jun / biosynthesis RNA, Messenger / biosynthesis Transcription, Genetic Transfection Tumor Cells, Cultured U937 Cells / enzymology*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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1 R01 HL63891-01A2/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3' Untranslated Regions; 0/Antigens, CD18; 0/Integrin alphaXbeta2; 0/Lymphocyte Function-Associated Antigen-1; 0/Macrophage-1 Antigen; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; EC 1.13.12.-/Luciferases; EC 2.7.11.1/protein kinase C zeta; EC 2.7.11.13/Protein Kinase C |
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