Matches in SemOpenAlex for { <https://semopenalex.org/work/W3017002183> ?p ?o ?g. }
Showing items 1 to 77 of
77
with 100 items per page.
- W3017002183 endingPage "1" @default.
- W3017002183 startingPage "1" @default.
- W3017002183 abstract "The microphthalmia-associated transcription factor (MITF) is a master regulator of development and differentiation within the melanocyte lineage. However, aberrant MITF activity can lead to multiple malignancies such as skin cancer, where it plays a key role in modulating the proliferation and invasiveness of melanoma. MITF is a basic helix-loop-helix leucine zipper transcription factor that binds to specific gene promoters via a central DNA-binding domain. MITF also recruits transcriptional co-activators, such as the histone acetyltransferase CREB-binding protein and its homologue p300 (CBP/p300) through an N-terminal acidic transactivation domain (TAD), however the details of these interactions are not yet fully understood. In order to gain insight into the mechanisms of gene regulation by MITF, we investigated the structure and functional interaction between MITF-TAD and the transcription adapter putative zinc finger (TAZ2) domain of CBP/p300. In mammalian-one-hybrid assays MITF transcriptional activity was enhanced in the presence of co-transfected CBP/p300 and abolished upon deletion of residues within the MITF-TAD. Peptide microarrays indicated that no one residue of MITF is essential for TAZ2 binding, however, deletion of multiple residues in MITF-TAD ablated its ability to bind TAZ2. NMR-based chemical shift mapping experiments determined that MITF-TAD interacts with the same surface of TAZ2 as the adenoviral protein E1A, which has been shown to inhibit MITF function. We determined that E1A and MITF-TAD directly compete for CBP/p300 through the TAZ2 domain using NMR-based titrations, pulldown, and mammalian-hybrid assays. Furthermore, we used qPCR to measure the effect of disrupting these interactions on the transcription of MITF-specific target genes in melanoma-derived cell lines. Understanding mechanistic details regarding the interaction between MITF and its co-activators is fundamental to our understanding of gene regulation by MITF and may outline a potential new strategy to inhibit MITF function. Support or Funding Information This research was funded by the Beatrice Hunter Cancer Research Institute, Nova Scotia Heath Research Foundation Scotia Scholars Award, a Canadian Institutes of Health Research studentship, Dalhousie Nova Scotia Graduate Scholarship, and Izaak Walton Killam Predoctoral Scholarship." @default.
- W3017002183 created "2020-04-24" @default.
- W3017002183 creator A5000938225 @default.
- W3017002183 creator A5016742300 @default.
- W3017002183 creator A5021657682 @default.
- W3017002183 creator A5025445331 @default.
- W3017002183 creator A5035774541 @default.
- W3017002183 creator A5063469638 @default.
- W3017002183 date "2020-04-01" @default.
- W3017002183 modified "2023-09-25" @default.
- W3017002183 title "Structural and Functional Insights into TAZ2‐mediated CBP/p300 Recruitment by the Melanogenic Transcription Factor MITF" @default.
- W3017002183 doi "https://doi.org/10.1096/fasebj.2020.34.s1.04156" @default.
- W3017002183 hasPublicationYear "2020" @default.
- W3017002183 type Work @default.
- W3017002183 sameAs 3017002183 @default.
- W3017002183 citedByCount "0" @default.
- W3017002183 crossrefType "journal-article" @default.
- W3017002183 hasAuthorship W3017002183A5000938225 @default.
- W3017002183 hasAuthorship W3017002183A5016742300 @default.
- W3017002183 hasAuthorship W3017002183A5021657682 @default.
- W3017002183 hasAuthorship W3017002183A5025445331 @default.
- W3017002183 hasAuthorship W3017002183A5035774541 @default.
- W3017002183 hasAuthorship W3017002183A5063469638 @default.
- W3017002183 hasBestOaLocation W30170021831 @default.
- W3017002183 hasConcept C104317684 @default.
- W3017002183 hasConcept C12652872 @default.
- W3017002183 hasConcept C1292079 @default.
- W3017002183 hasConcept C138885662 @default.
- W3017002183 hasConcept C153911025 @default.
- W3017002183 hasConcept C1629964 @default.
- W3017002183 hasConcept C177504595 @default.
- W3017002183 hasConcept C179926584 @default.
- W3017002183 hasConcept C185592680 @default.
- W3017002183 hasConcept C41895202 @default.
- W3017002183 hasConcept C54355233 @default.
- W3017002183 hasConcept C6174537 @default.
- W3017002183 hasConcept C86339819 @default.
- W3017002183 hasConcept C86803240 @default.
- W3017002183 hasConcept C94966510 @default.
- W3017002183 hasConcept C95444343 @default.
- W3017002183 hasConceptScore W3017002183C104317684 @default.
- W3017002183 hasConceptScore W3017002183C12652872 @default.
- W3017002183 hasConceptScore W3017002183C1292079 @default.
- W3017002183 hasConceptScore W3017002183C138885662 @default.
- W3017002183 hasConceptScore W3017002183C153911025 @default.
- W3017002183 hasConceptScore W3017002183C1629964 @default.
- W3017002183 hasConceptScore W3017002183C177504595 @default.
- W3017002183 hasConceptScore W3017002183C179926584 @default.
- W3017002183 hasConceptScore W3017002183C185592680 @default.
- W3017002183 hasConceptScore W3017002183C41895202 @default.
- W3017002183 hasConceptScore W3017002183C54355233 @default.
- W3017002183 hasConceptScore W3017002183C6174537 @default.
- W3017002183 hasConceptScore W3017002183C86339819 @default.
- W3017002183 hasConceptScore W3017002183C86803240 @default.
- W3017002183 hasConceptScore W3017002183C94966510 @default.
- W3017002183 hasConceptScore W3017002183C95444343 @default.
- W3017002183 hasIssue "S1" @default.
- W3017002183 hasLocation W30170021831 @default.
- W3017002183 hasOpenAccess W3017002183 @default.
- W3017002183 hasPrimaryLocation W30170021831 @default.
- W3017002183 hasRelatedWork W1987464279 @default.
- W3017002183 hasRelatedWork W1996113686 @default.
- W3017002183 hasRelatedWork W1997889534 @default.
- W3017002183 hasRelatedWork W2010547812 @default.
- W3017002183 hasRelatedWork W2032512715 @default.
- W3017002183 hasRelatedWork W2048947200 @default.
- W3017002183 hasRelatedWork W2414026108 @default.
- W3017002183 hasRelatedWork W2619252722 @default.
- W3017002183 hasRelatedWork W4239204209 @default.
- W3017002183 hasRelatedWork W2093199710 @default.
- W3017002183 hasVolume "34" @default.
- W3017002183 isParatext "false" @default.
- W3017002183 isRetracted "false" @default.
- W3017002183 magId "3017002183" @default.
- W3017002183 workType "article" @default.