Inhibition of caspase-2 translation by the mrna binding protein hur : a novel path of therapy resistance in colon carcinoma cells?

  • An increased expression and cytoplasmic abundance of the ubiquitous RNA binding protein human antigen R (HuR) is critically implicated in the dysregulated control of post-transcriptional gene expression during colorectal cancer development and is frequently associated with a high grade of malignancy and therapy resistance. Regardless of the fact that HuR elicits a broad cell survival program by increasing the stability of mRNAs coding for prominent anti-apoptotic factors, recent data suggest that HuR is critically involved in the regulation of translation, particularly, in the internal ribosome entry site (IRES) controlled translation of cell death regulatory proteins. Accordingly, data from human colon carcinoma cells revealed that HuR maintains constitutively reduced protein and activity levels of caspase-2 through negative interference with IRES-mediated translation. This review covers recent advances in the understanding of mechanisms underlying HuR’s modulatory activity on IRES-triggered translation. With respect to the unique regulatory features of caspase-2 and its multiple roles (e.g., in DNA-damage-induced apoptosis, cell cycle regulation and maintenance of genomic stability), the pathophysiological consequences of negative caspase-2 regulation by HuR and its impact on therapy resistance of colorectal cancers will be discussed in detail. The negative HuR-caspase-2 axis may offer a novel target for tumor sensitizing therapies.

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Author:Wolfgang Eberhardt, Usman Nasrullah, Kristina Häußler
Pubmed Id:
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/07/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/08/26
Tag:DNA damage response; RNA binding proteins; caspase-2; cell survival mechanisms; colorectal cancer; human antigen R (HuR); internal ribosomal entry site (IRES)
Issue:8, Art. 797
Page Number:21
First Page:1
Last Page:21
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0