
Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 …
Nov 1, 2019 · Here, we reveal the oncogenic role of a novel MYCN target and binding protein, proliferation-associated 2AG4 (PA2G4). Chromatin immunoprecipitation studies demonstrated that MYCN occupies the PA2G4 gene promoter, stimulating transcription.
Inhibitors of the Oncogenic PA2G4-MYCN Protein-Protein Interface
Mar 17, 2023 · In neuroblastoma cells, PA2G4 is a transactivation target for MYCN. PA2G4 directly binds to and stabilises MYCN by preventing its ubiquitin-mediated proteolysis . Inhibition of PA2G4 and MYCN binding by WS6 can reduce levels of both proteins and neuroblastoma tumorigenicity in vitro and in vivo.
Inhibitors of the Oncogenic PA2G4-MYCN Protein-Protein Interface
Mar 17, 2023 · MYCN is a major oncogenic driver for neuroblastoma tumorigenesis, yet there are no direct MYCN inhibitors. We have previously identified PA2G4 as a direct protein-binding partner of MYCN and drive neuroblastoma tumorigenesis.
Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 …
Nov 1, 2019 · Here, we reveal the oncogenic role of a novel MYCN target and binding protein, proliferation-associated 2AG4 (PA2G4). Chromatin immunoprecipitation studies demonstrated that MYCN occupies the PA2G4 gene promoter, stimulating transcription.
A structural view of PA2G4 isoforms with opposing functions in …
Our studies revealed that PA2G4 was able to bind directly to MYCN, leading to an oncogenic forward feedback loop of high expression levels of PA2G4-p48 and MYCN proteins . PA2G4-p48 has also been implicated in the tumorigenesis of oral squamous cell carcinoma (OSCC).
We have identified a protein called PA2G4, which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound WS6 and its analogous, which inhibits PA2G4 and MYCN protein levels and reduces tumour cell growth.
(PDF) Drugging MYCN oncogenic signalling through the MYCN-PA2G4 …
Sep 9, 2019 · Here, we reveal the oncogenic role of a novel MYCN target and binding protein, proliferation-associated 2AG4 (PA2G4). Chromatin immunoprecipitation studies demonstrated that MYCN occupies the...
Drugging MYCN oncogenic signalling through the MYCN-PA2G4 …
Sep 9, 2019 · Treated tumors showed reduced levels of both MYCN and PA2G4. Our findings demonstrate a critical role for PA2G4 as cofactor in MYCN-driven neuroblastoma and highlight competitive inhibition of the PA2G4-MYCN protein binding as …
(PDF) Drugging MYCN oncogenic signalling through the MYCN-PA2G4 …
To expand our understanding of how small molecules interfere with MYCN, we have now analyzed the direct binding of 10058-F4, as well as three of its analogs; #474, #764 and 10058 …
Targeting MYCN in Pediatric and Adult Cancers - Frontiers
Feb 8, 2021 · Co-immunoprecipitation results show that a MYCN deletion mutant (AA82–254) binds strongly to PA2G4, and further studies show that a 14 AA MYCN oligopeptide (AA246–259) sequence contributes to this protein-protein interaction .