Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-5-24
pubmed:abstractText
CDKN2B (INK4B), which encodes the cyclin-dependent kinase inhibitor p15(INK4b), is up-regulated by many cytokines found in hematopoietic environments in vivo. In human acute myeloid leukemias (AMLs), it is inactivated with high frequency. To gain insight into the regulatory pathways leading to the normal activation of p15(Ink4b) expression, we examined interferon beta (IFNbeta)-induced transcription. Using reporter gene assays in murine myeloid cells M1, we determined that a 328-bp fragment, located 117 to 443 bp upstream of the translation initiation site, was sufficient to activate transcription. Both the interferon consensus sequence-binding protein/interferon regulatory factor 8 (ICSBP/IRF-8) and PU.1 were able to increase transcription from this region. It was determined that both ICSBP and PU.1 must bind to DNA to form a stable PU.1/ICSBP binding complex. Interestingly, introduction of the ICSBP into ICSBP-null Tot2 cells led to a significant increase in p15(Ink4b) RNA expression. This regulation of the Ink4b promoter is apparently myeloid specific because both ICSBP and PU.1 are myeloid commitment factors. Importantly, this provides a mechanism to explain in part the tumor suppressor activity of ICSBP, since ICSBP-deficient mice develop a chronic myelogenous leukemia (CML)-like disease and a high percentage of human AML and CML lack ICSBP transcripts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cdkn2b protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-8, http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4142-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14976051-Acute Disease, pubmed-meshheading:14976051-Animals, pubmed-meshheading:14976051-Antineoplastic Agents, pubmed-meshheading:14976051-Base Sequence, pubmed-meshheading:14976051-Cell Cycle Proteins, pubmed-meshheading:14976051-Cell Line, Tumor, pubmed-meshheading:14976051-Cyclin-Dependent Kinase Inhibitor p15, pubmed-meshheading:14976051-Gene Deletion, pubmed-meshheading:14976051-Gene Expression Regulation, pubmed-meshheading:14976051-Hematopoietic Stem Cells, pubmed-meshheading:14976051-Interferon Regulatory Factors, pubmed-meshheading:14976051-Interferon-beta, pubmed-meshheading:14976051-Leukemia, Myeloid, pubmed-meshheading:14976051-Mice, pubmed-meshheading:14976051-Molecular Sequence Data, pubmed-meshheading:14976051-Myeloid Cells, pubmed-meshheading:14976051-Promoter Regions, Genetic, pubmed-meshheading:14976051-Proto-Oncogene Proteins, pubmed-meshheading:14976051-Repressor Proteins, pubmed-meshheading:14976051-Trans-Activators, pubmed-meshheading:14976051-Transcription, Genetic, pubmed-meshheading:14976051-Tumor Suppressor Proteins, pubmed-meshheading:14976051-Up-Regulation
pubmed:year
2004
pubmed:articleTitle
The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15(Ink4b) in murine myeloid cells.
pubmed:affiliation
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892-4263, USA.
pubmed:publicationType
Journal Article