Linked Life Data

9819223

Source:http://linkedlifedata.com/resource/pubmed/id/9819223

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
1998-12-17
pubmed:abstractText
Several eukaryotic cellular proteins recognize DNA modified by the anticancer drug cisplatin (cis-diamminedichloroplatinum(II) or cis-DDP); among these proteins is a class of DNA-binding molecules containing the HMG (high-mobility group) box DNA recognition motif. We have previously reported the extraordinarily high binding activity to cisplatin adducts by human upstream binding factor (hUBF), an HMG box containing transcription factor that stimulates ribosomal RNA synthesis (Treiber et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 5672-5676). In the present study, we discovered that (1) hUBF interacted selectively with DNA lesions formed by therapeutically effective platinum compounds [Pt(en)Cl2] and [Pt(dach)Cl2], in addition to the lesions formed by cis-DDP, suggesting a possible association with their anticancer effect; (2) multiple HMG boxes contributed additively to the hUBF-adduct interaction, providing a possible explanation for the unusually high affinity of hUBF for cis-DDP adducts as compared to the lower affinities of other HMG box proteins; and (3) ribosomal RNA transcription in a reconstituted system is specifically inhibited in the presence of cis-DDP adducts. In this third experiment, a ratio of adducts/promoter of approximately 4:1 completely abolished the transcription activated by hUBF. Taken together, these data lend support to the view that transcription factors involved in cellular growth regulation, such as ribosomal RNA transcription, may be hijacked by cis-DDP adducts resulting in functional inhibition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin, http://linkedlifedata.com/resource/pubmed/chemical/D 17872, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ethylenediamines, http://linkedlifedata.com/resource/pubmed/chemical/High Mobility Group Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Organoplatinum Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Pol1 Transcription Initiation..., http://linkedlifedata.com/resource/pubmed/chemical/RNA, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/cisplatin-DNA adduct, http://linkedlifedata.com/resource/pubmed/chemical/dichloro-1,2-diaminocyclohexane..., http://linkedlifedata.com/resource/pubmed/chemical/transcription factor UBF, http://linkedlifedata.com/resource/pubmed/chemical/transplatin
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16307-15
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Cisplatin-DNA adducts inhibit ribosomal RNA synthesis by hijacking the transcription factor human upstream binding factor.
pubmed:affiliation
Department of Chemistry, Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.