Academic Journal
Post-Translational Regulation of ARF: Perspective in Cancer
| Title: | Post-Translational Regulation of ARF: Perspective in Cancer |
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| Authors: | Jinho Seo, Daehyeon Seong, Seung Ri Lee, Doo-Byoung Oh, Jaewhan Song |
| Source: | Biomolecules, Vol 10, Iss 8, p 1143 (2020) |
| Publisher Information: | MDPI AG, 2020. |
| Publication Year: | 2020 |
| Collection: | LCC:Microbiology |
| Subject Terms: | ARF, post-translational modification, transcriptional regulation, tumor suppressor, cancer, p14, Microbiology, QR1-502 |
| More Details: | Tumorigenesis can be induced by various stresses that cause aberrant DNA mutations and unhindered cell proliferation. Under such conditions, normal cells autonomously induce defense mechanisms, thereby stimulating tumor suppressor activation. ARF, encoded by the CDKN2a locus, is one of the most frequently mutated or deleted tumor suppressors in human cancer. The safeguard roles of ARF in tumorigenesis are mainly mediated via the MDM2-p53 axis, which plays a prominent role in tumor suppression. Under normal conditions, low p53 expression is stringently regulated by its target gene, MDM2 E3 ligase, which induces p53 degradation in a ubiquitin-proteasome-dependent manner. Oncogenic signals induced by MYC, RAS, and E2Fs trap MDM2 in the inhibited state by inducing ARF expression as a safeguard measure, thereby activating the tumor-suppressive function of p53. In addition to the MDM2-p53 axis, ARF can also interact with diverse proteins and regulate various cellular functions, such as cellular senescence, apoptosis, and anoikis, in a p53-independent manner. As the evidence indicating ARF as a key tumor suppressor has been accumulated, there is growing evidence that ARF is sophisticatedly fine-tuned by the diverse factors through transcriptional and post-translational regulatory mechanisms. In this review, we mainly focused on how cancer cells employ transcriptional and post-translational regulatory mechanisms to manipulate ARF activities to circumvent the tumor-suppressive function of ARF. We further discussed the clinical implications of ARF in human cancer. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 10081143 2218-273X |
| Relation: | https://www.mdpi.com/2218-273X/10/8/1143; https://doaj.org/toc/2218-273X |
| DOI: | 10.3390/biom10081143 |
| Access URL: | https://doaj.org/article/9d7eb6b8731645c0a822b6bea798b419 |
| Accession Number: | edsdoj.9d7eb6b8731645c0a822b6bea798b419 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 10081143 2218273X |
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| DOI: | 10.3390/biom10081143 |
| Published in: | Biomolecules |
| Language: | English |