title: 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 alpha. 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 alpha-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-RARalpha fusion protein.
authors.affiliation: Centre for Structural Biology, Imperial College of Science, Technology and Medicine, Flowers Building, Armstrong Road, London SW7 2AZ, UK.
authors.forename: K
authors.initials: K
authors.lastname: Jensen
authors.forename: C
authors.initials: C
authors.lastname: Shiels
authors.forename: P S
authors.initials: PS
authors.lastname: Freemont
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D008025:Ligases / Q000235:genetics; D008868:Microtubule Proteins; D009363:Neoplasm Proteins / Q000145:classification* / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D020033:Protein Isoforms / Q000145:classification / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D013329:Structure-Activity Relationship; D009626:Terminology as Topic; D014157:Transcription Factors / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D008868:Microtubule Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C109052:MID1 protein, human; C411745:TRIM37 protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases