TY  - JOUR
A1  - Ahmad, Khalil
A1  - Scholz, Bastian
A1  - Capelo, Ricardo
A1  - Schweighöfer, Ilona
A1  - Kahnt, Astrid Stefanie
A1  - Marschalek, Rolf
A1  - Steinhilber, Dieter
T1  - AF4 and AF4-MLL mediate transcriptional elongation of 5-lipoxygenase mRNA by 1, 25-dihydroxyvitamin D3
T2  - OncoTarget
N2  - The human 5-lipoxygenase (5-LO), encoded by the ALOX5 gene, is the key enzyme in the formation of pro-inflammatory leukotrienes. ALOX5 gene transcription is strongly stimulated by calcitriol (1α, 25-dihydroxyvitamin D3) and TGFβ (transforming growth factor-β). Here, we investigated the influence of MLL (activator of transcript initiation), AF4 (activator of transcriptional elongation) as well as of the leukemogenic fusion proteins MLL-AF4 (ectopic activator of transcript initiation) and AF4-MLL (ectopic activator of transcriptional elongation) on calcitriol/TGFβ-dependent 5-LO transcript elongation. We present evidence that the AF4 complex directly interacts with the vitamin D receptor (VDR) and promotes calcitriol-dependent ALOX5 transcript elongation. Activation of transcript elongation was strongly enhanced by the AF4-MLL fusion protein but was sensitive to Flavopiridol. By contrast, MLL-AF4 displayed no effect on transcriptional elongation. Furthermore, HDAC class I inhibitors inhibited the ectopic effects caused by AF4-MLL on transcriptional elongation, suggesting that HDAC class I inhibitors are potential therapeutics for the treatment of t(4;11)(q21;q23) leukemia.
KW  - 5-lipoxygenase
KW  - MLL
KW  - AF4
KW  - calcitriol
KW  - HDAC
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/41895
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-418954
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694866
UR  - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=4703
SN  - 1949-2553
N1  - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
VL  - 6
IS  - 28
SP  - 25784
EP  - 25800
PB  - Impact Journals LLC
CY  - [S. l.]
ER  -