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 suering 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 a. 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 dier in their C-terminal sequences. The N-terminal region harbours a RING-®nger, two B-boxes and a predicted a-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 antiviral activities. In APL oligomerization mediated by the RBCC/TRIM motif is essential for the transformation potential of the PML-RARa fusion protein. Oncogene (2001) 20, 7223 ± 7233.

SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML

“…In this context, it additionally remains completely elusive how the specificity of E1B-55K PML-IV/V interaction is achieved, as no unique protein sequences can be found in this two PML isoforms. Both harbour the exons 1-6, which are actually present in all PML proteins except for PML-VII, the exon 7a, which again is additionally present in PML-I/-II/-III, and their own unique C-terminus (Jensen et al, 2001). However, as a similar phenomenon has been described for HPV E6 (Guccione et al, 2004), it seems that disruption and/or facilitation of PML nuclear bodies, specific PML isoforms and/or PML-associated proteins may represent a general mechanism that might also have a role in viral-mediated oncogenesis.…”

“…Although human cell lines exhibit a complicated system expressing at least seven distinguishable PML isoforms (Jensen et al, 2001), we decided to analyse the capability of E1B-55K to interact with the human orthologs of rodent PML as very less is known about the expression of distinct PML isoforms in rats. Therefore, we transfected H1299 cells with E1B-55K-wt and plasmids encoding for human PML isoforms I-VI.…”

“…N-terminal flag-tagged human PML isoforms I-VI were expressed from pLKO.1-puro vector (kindly provided by R Everett). All PML isoforms are termed according to the nomenclature of Jensen et al (2001) as PML-I (AAG50180), PML-II (AF230410), PML-III (S50913), PML-IV(AAG50185), PML-V (AAG50181) and PML-VI (AAG50184).…”

PML4 induces differentiation by Myc destabilization

“…The PML protein exists in seven major isoforms that are generated by alternative splicing of the messenger RNA (Jensen et al, 2001). All PML isoforms share RING, B-box and coiled-coil domains but differ in their C-terminal regions.…”

Implication des corps nucléaires PML dans l’immunité intrinsèque et innée

“…Dans cette revue, nous discutons l'implication des isoformes de PML dans la réponse interféron et la défense antivirale, à l'interface des immunités intrinsèque et innée. (Figure 1) [6,7]. La variabilité de la région carboxy-terminale des isoformes de PML leur permet d'interagir avec différents partenaires et leur confère donc des fonctions spécifiques [6].…”