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Sci Rep. 2019 May 27;9(1):7901. doi: 10.1038/s41598-019-44359-0.

A repetitive acidic region contributes to the extremely rapid degradation of the cell-context essential protein TRIM52.

Author information

1
Department of Microbiology, Immunobiology, and Genetics, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9, 1030, Vienna, Austria.
2
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090, Vienna, Austria.
3
Department of Microbiology, Immunobiology, and Genetics, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9, 1030, Vienna, Austria. gijs.versteeg@univie.ac.at.

Abstract

Tripartite motif protein 52 (TRIM52) is a non-canonical TRIM family member harbouring the largest RING domain encoded in the human genome. In humans TRIM52 is conserved and has been under positive selection pressure, yet it has been lost in many non-primates. Competitive cell fitness assays demonstrated that TRIM52 ablation reduces cellular fitness in multiple different cell types. To better understand how this cell-essential factor is controlled, we investigated how expression of this non-canonical protein is regulated. Here, we show that TRIM52 mRNA is constitutively expressed from an intergenic region preceding the TRIM52 gene. Yet, TRIM52 protein is rapidly turned-over by the proteasome with a 3.5-minute half-life, one of the shortest in the human proteome. Consistent with this extremely rapid degradation rate, all three TRIM52 domains were identified to contribute to its instability. Intriguingly, a repetitive acidic loop in the RING domain was identified as one of the main destabilizing regions, which was unexpected given the prevailing notion that these sequences are poor proteasome substrates. This work indicates that the effect of such repetitive acidic regions on proteasomal degradation depends on the protein context, and it identifies TRIM52 as an attractive model protein to study what these contextual properties are.

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