| Lack of Bcl11b tumor suppressor results in vulnerability to DNA replication stress and damages. | |
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MedLine Citation:
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PMID: 17369851 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bcl11b/Rit1 is involved in T-cell development and undergoes chromosomal rearrangements in human T-cell leukemias. Thymocytes of Bcl11b(-/-) newborn mice exhibit apoptosis at a certain developmental stage when thymocytes re-enter into the cell-cycle. Here, we show that Bcl11b-knockdown T-cell lines, when exposed to growth stimuli, exhibited apoptosis at the S phase with concomitant decreases in a cell-cycle inhibitor, p27 and an antiapoptotic protein, Bcl-xL, owing to transcriptional repression. This repression was a likely consequence of the impairment of Sirt1, a nicotinamide adenine dinucleotide-dependent deacetylase associating with Bcl11b. Activation of the apoptotic process cleaved the mediator protein, Claspin, and inhibited phosphorylation of cell-cycle checkpoint kinase 1 (Chk1) that plays a central role in sensing and responding to incomplete replication. Bcl11b(-/-) thymocytes also failed to phosphorylate Chk1 when UV irradiated. These results implicate Bcl11b in the remedy for DNA replication stress and maintenance of genomic integrity. |
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Authors:
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K Kamimura; Y Mishima; M Obata; T Endo; Y Aoyagi; R Kominami |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-19 |
Journal Detail:
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Title: Oncogene Volume: 26 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-08-30 Completed Date: 2007-10-11 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 5840-50 Citation Subset: IM |
Affiliation:
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Department of Molecular Genetics, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata 951-8510, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Apoptosis Cell Cycle DNA Replication* DNA-Binding Proteins / genetics, physiology* Humans Jurkat Cells Mice Mice, Inbred BALB C Mice, Knockout Protein Kinases / metabolism Repressor Proteins / genetics, physiology* Sirtuin 1 Sirtuins / metabolism Tumor Suppressor Proteins / genetics, physiology* bcl-X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/BCL11B protein, human; 0/Bcl11b protein, mouse; 0/DNA-Binding Proteins; 0/Repressor Proteins; 0/Tumor Suppressor Proteins; 0/bcl-X Protein; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Checkpoint kinase 1; EC 3.5.1.-/SIRT1 protein, human; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1; EC 3.5.1.-/Sirtuins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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