Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3' Untranslated Region.

Fernández Marrero, Yuniel; Bachmann, Daniel; Lauber, Emanuel; Kaufmann, Thomas (2018). Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3' Untranslated Region. iScience, 9, pp. 461-474. Elsevier 10.1016/j.isci.2018.11.005

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BCL-2-related ovarian killer (BOK) is a pro-apoptotic BAX-like member of the BCL-2 family with suggested tumor suppressor activity. The molecular mechanisms regulating BOK expression are poorly understood and fail to explain a frequent lack of concordance between protein and transcript levels. Here, we describe a potent post-transcriptional mechanism that negatively regulates BOK expression mediated by conserved (AU/U)-rich elements within its 3' UTR. Using proteomics approaches we identified TRIM28 as a key component associating with U-rich elements in the human BOK 3' UTR, resulting in a dramatic reduction of BOK expression. TRIM28 is overexpressed in several cancers, correlating with poor patient outcome, whereas the BOK locus is frequently deleted or its expression downregulated in human cancers. Data mining indicated that, for certain cancers, high TRIM28 and low BOK expression are significantly correlated in the stratum of patients with the worst survival, suggesting that this mechanism might be of potential therapeutic value.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Fernández Marrero, Yuniel; Bachmann, Daniel and Kaufmann, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2589-0042

Publisher:

Elsevier

Language:

English

Submitter:

Celine Joray

Date Deposited:

28 Dec 2018 15:13

Last Modified:

01 Dec 2020 15:20

Publisher DOI:

10.1016/j.isci.2018.11.005

PubMed ID:

30471638

Uncontrolled Keywords:

Cancer Molecular Mechanism of Gene Regulation

BORIS DOI:

10.7892/boris.122133

URI:

https://boris.unibe.ch/id/eprint/122133

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