YAP1 oncogene and its eight isoforms


Fernandez-L et al.1 and Liu et al.2 reported functional analyses of the human YAP1 gene using overexpression of its complementary DNA (cDNA) in various cell lines. Interestingly, in these reports one of the eight existing isoforms of YAP1 cDNA was used, namely YAP1 encoding 504 amino acid long protein. This isoform of YAP1 is generated by the splicing of exon 6 within the region of the transcript that encodes transcriptional activation domain (TAD) (Figure 1 and Gaffney et al.3). Other reports, in which the human YAP1 gene was interrogated in cells as a transfected cDNA, used different isoforms of YAP1, which encoded either 454 or 488 amino acid long proteins.4, 5 The YAP1-454 isoform was shown to signal differently from the YAP1-488 isoform (see discussion in Gaffney et al.3). Moreover, YAP1-488 isoform has an intact leucine zipper within its TAD domain, unlike YAP1-504, whose leucine zipper is interrupted by the insertion of 16 amino acids encoded by exon 6. Because of these structural and signaling differences, it is important to report which isoform of YAP1 is used in overexpression studies. This letter is to propose a unified nomenclature for YAP1 oncogene cDNA constructs as YAP1-XXX where XXX are the number of amino acids encoded by a given cDNA (Figure 1). Alternatively, YAP1-1α, β, γ, δ and YAP1-2 α, β, γ, δ could also be used.

Figure 1

Schematic representation of four isoforms of YAP1-1 and four isoforms of YAP1-2. The number of amino acids encoded by each isoform is shown on the right side. The location of WW domains in the amino-terminal region of YAP1 is shown by black arrows and amino acid numbers. Within the TAD (transcription activation domain) there is a leucine zipper (white rectangle) in YAP1-450 and YAP1-488. The leucine zipper is interrupted at position 290 in YAP1-1 isoforms and at position 328 in YAP1-2 isoforms with the exon 5 extention (black rectangle) and/or exon 6 (gray rectangle). Modified from Gaffney et al.3


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This work was supported by grants from PA Breast Cancer Coalition (#RFA60707; RFA9200903) and by Geisinger Clinic.

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Correspondence to M Sudol.

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Sudol, M. YAP1 oncogene and its eight isoforms. Oncogene 32, 3922 (2013). https://doi.org/10.1038/onc.2012.520

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