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PML protein isoforms and the RBCC/TRIM motif

Abstract

PML is a component of a multiprotein complex, termed nuclear bodies, and the PML protein was originally discovered in patients suffering from acute promyelocytic leukaemia (APL). APL is associated with a reciprocal chromosomal translocation of chromosomes 15 and 17, which results in a fusion protein comprising PML and the retinoic acid receptor α. The PML genomic locus is approximately 35 kb and is subdivided into nine exons. A large number of alternative spliced transcripts are synthesized from the PML gene, resulting in a variety of PML proteins ranging in molecular weight from 48–97 kDa. In this review we summarize the data on the known PML isoforms and splice variants and present a new unifying nomenclature. Although, the function/s of the PML variants are unclear, all PML isoforms contain an identical N-terminal region, suggesting that these sequences are indispensable for function, but differ in their C-terminal sequences. The N-terminal region harbours a RING-finger, two B-boxes and a predicted α-helical Coiled-Coil domain, that together form the RBCC/TRIM motif found in a large family of proteins. In PML this motif is essential for PML nuclear body formation in vivo and PML-homo and hetero interactions conferring growth suppressor, apoptotic and anti-viral activities. In APL oligomerization mediated by the RBCC/TRIM motif is essential for the transformation potential of the PML-RARα fusion protein.

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Acknowledgements

We thank Kathy Borden and Thomas Sternsdorf for critical reading of the manuscript and helpful discussions. We also thank all our colleagues for contributing to the proposed nomenclature for the PML isoforms.

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Correspondence to Paul S Freemont.

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Jensen, K., Shiels, C. & Freemont, P. PML protein isoforms and the RBCC/TRIM motif. Oncogene 20, 7223–7233 (2001). https://doi.org/10.1038/sj.onc.1204765

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