GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2
dc.contributor.author | Yang, Zhongfa | |
dc.contributor.author | Zhang, Haojian | |
dc.contributor.author | Ma, Leyuan | |
dc.contributor.author | Peng, Cong | |
dc.contributor.author | Chen, Yaoyu | |
dc.contributor.author | Wang, Junling | |
dc.contributor.author | Green, Michael R. | |
dc.contributor.author | Li, Shaoguang | |
dc.contributor.author | Rosmarin, Alan G. | |
dc.date | 2022-08-11T08:10:15.000 | |
dc.date.accessioned | 2022-08-23T17:01:25Z | |
dc.date.available | 2022-08-23T17:01:25Z | |
dc.date.issued | 2013-02-05 | |
dc.date.submitted | 2013-02-14 | |
dc.identifier.citation | Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2312-7. doi: 10.1073/pnas.1212904110. <a href="http://dx.doi.org/10.1073/pnas.1212904110">Link to article on publisher's site</a> | |
dc.identifier.issn | 0027-8424 (Linking) | |
dc.identifier.doi | 10.1073/pnas.1212904110 | |
dc.identifier.pmid | 23345428 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/44005 | |
dc.description.abstract | Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. Transformation of HSCs by the breakpoint cluster region-ABL tyrosine kinase (BCR-ABL) oncogene causes chronic myelogenous leukemia (CML). The E-twenty six (ets) transcription factor GA binding protein (GABP) is a tetrameric transcription factor complex that contains GABPalpha and GABPbeta proteins. Deletion in bone marrow of Gabpa, the gene that encodes the DNA-binding component, caused cell cycle arrest in HSCs and profound loss of hematopoietic progenitor cells. Loss of Gabpalpha prevented development of CML, although mice continued to generate BCR-ABL-expressing Gabpalpha-null cells for months that were serially transplantable and contributed to all lineages in secondary recipients. A bioinformatic screen identified the serine-threonine kinase protein kinase D2 (PRKD2) as a potential effector of GABP in HSCs. Prkd2 expression was markedly reduced in Gabpalpha-null HSCs and progenitor cells. Reduced expression of PRKD2 or pharmacologic inhibition decreased cell cycling, and PRKD2 rescued growth of Gabpalpha-null BCR-ABL-expressing cells. Thus, GABP is required for HSC cell cycle entry and CML development through its control of PRKD2. This offers a potential therapeutic target in leukemia. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23345428&dopt=Abstract">Link to Article in PubMed</a> | |
dc.relation.url | http://dx.doi.org/10.1073/pnas.1212904110 | |
dc.rights | <p>Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.</p> | |
dc.subject | GA-Binding Protein Transcription Factor | |
dc.subject | Leukemia, Myelogenous, Chronic, BCR-ABL Positive | |
dc.subject | Biochemistry, Biophysics, and Structural Biology | |
dc.subject | Genetics and Genomics | |
dc.subject | Hematology | |
dc.subject | Hemic and Lymphatic Diseases | |
dc.subject | Neoplasms | |
dc.subject | Oncology | |
dc.title | GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2 | |
dc.type | Journal Article | |
dc.source.journaltitle | Proceedings of the National Academy of Sciences of the United States of America | |
dc.source.volume | 110 | |
dc.source.issue | 6 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1212&context=pgfe_pp&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/pgfe_pp/212 | |
dc.identifier.contextkey | 3703918 | |
refterms.dateFOA | 2022-08-23T17:01:25Z | |
html.description.abstract | <p>Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. Transformation of HSCs by the breakpoint cluster region-ABL tyrosine kinase (BCR-ABL) oncogene causes chronic myelogenous leukemia (CML). The E-twenty six (ets) transcription factor GA binding protein (GABP) is a tetrameric transcription factor complex that contains GABPalpha and GABPbeta proteins. Deletion in bone marrow of Gabpa, the gene that encodes the DNA-binding component, caused cell cycle arrest in HSCs and profound loss of hematopoietic progenitor cells. Loss of Gabpalpha prevented development of CML, although mice continued to generate BCR-ABL-expressing Gabpalpha-null cells for months that were serially transplantable and contributed to all lineages in secondary recipients. A bioinformatic screen identified the serine-threonine kinase protein kinase D2 (PRKD2) as a potential effector of GABP in HSCs. Prkd2 expression was markedly reduced in Gabpalpha-null HSCs and progenitor cells. Reduced expression of PRKD2 or pharmacologic inhibition decreased cell cycling, and PRKD2 rescued growth of Gabpalpha-null BCR-ABL-expressing cells. Thus, GABP is required for HSC cell cycle entry and CML development through its control of PRKD2. This offers a potential therapeutic target in leukemia.</p> | |
dc.identifier.submissionpath | pgfe_pp/212 | |
dc.contributor.department | Program in Gene Function and Expression | |
dc.contributor.department | Program in Molecular Medicine | |
dc.contributor.department | Department of Medicine, Division of Hematology/Oncology | |
dc.source.pages | 2312-7 |