| Autor: |
Seung Han Son, Min Young Kim, Sungwoo Choi, Ji Sook Kim, Yong Sang Lee, Sangwon Lee, Yeon Ju Lee, Jin Youn Lee, Seol Eui Lee, Young Su Lim, Dae Hyun Ha, Eonju Oh, Young‐Bin Won, Chang‐Jun Ji, Mi Ae Park, Boram Kim, Kyu Tae Byun, Min Sung Chung, Jaemin Jeong, Dongho Choi, Eun Jung Baek, Eung‐Ho Cho, Sang‐Bum Kim, A. Reum Je, Hee‐Seok Kweon, Hyun Sook Park, Dongsun Park, June Sung Bae, Se Jin Jang, Chae‐Ok Yun, Ji Hyung Chae, Jin‐Won Lee, Su‐Jae Lee, Chan Gil Kim, Ho Chul Kang, Vladimir N. Uversky, Chul Geun Kim |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Advanced Science, Vol 10, Iss 33, Pp n/a-n/a (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202305096 |
| Popis: |
Abstract Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof‐of‐principle evidence is presented that a cell‐penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene‐addicted cancer cells through transcription activity‐independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2‐p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome‐wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C‐resistant cancers. This study enhances the understanding of ACP52C‐induced cancer‐specific apoptosis induction and supports the use of ACP52C in anticancer drug development. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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