The Impact of Lens Epithelium-Derived Growth Factor p75 Dimerization on Its Tethering Function
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00583040" target="_blank" >RIV/61388963:_____/24:00583040 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/24:10487479
Result on the web
<a href="https://doi.org/10.3390/cells13030227" target="_blank" >https://doi.org/10.3390/cells13030227</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/cells13030227" target="_blank" >10.3390/cells13030227</a>
Alternative languages
Result language
angličtina
Original language name
The Impact of Lens Epithelium-Derived Growth Factor p75 Dimerization on Its Tethering Function
Original language description
The transcriptional co-activator lens epithelium-derived growth factor/p75 (LEDGF/p75) plays an important role in the biology of the cell and in several human diseases, including MLL-rearranged acute leukemia, autoimmunity, and HIV-1 infection. In both health and disease, LEDGF/p75 functions as a chromatin tether that interacts with proteins such as MLL1 and HIV-1 integrase via its integrase-binding domain (IBD) and with chromatin through its N-terminal PWWP domain. Recently, dimerization of LEDGF/p75 was shown, mediated by a network of electrostatic contacts between amino acids from the IBD and the C-terminal alpha 6-helix. Here, we investigated the functional impact of LEDGF/p75 variants on the dimerization using biochemical and cellular interaction assays. The data demonstrate that the C-terminal alpha 6-helix folds back in cis on the IBD of monomeric LEDGF/p75. We discovered that the presence of DNA stimulates LEDGF/p75 dimerization. LEDGF/p75 dimerization enhances binding to MLL1 but not to HIV-1 integrase, a finding that was observed in vitro and validated in cell culture. Whereas HIV-1 replication was not dependent on LEDGF/p75 dimerization, colony formation of MLLr-dependent human leukemic THP-1 cells was. In conclusion, our data indicate that intricate changes in the quaternary structure of LEDGF/p75 modulate its tethering function.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cells
ISSN
2073-4409
e-ISSN
2073-4409
Volume of the periodical
13
Issue of the periodical within the volume
3
Country of publishing house
CH - SWITZERLAND
Number of pages
22
Pages from-to
227
UT code for WoS article
001160361000001
EID of the result in the Scopus database
2-s2.0-85184740165