YAP1 oncogene and its eight isoforms

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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
figure1

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

References

  1. 1

    Fernandez-L A, Squatrito M, Northcott P, Awan A, Holland EC, Taylor MD et al. Oncogenic YAP promotes radioresistance and genomic instability in medulloblastomas through IGF2-mediated Akt activation. Oncogene 2012; 31: 1923–1937.

    CAS  Article  Google Scholar 

  2. 2

    Liu X, Yang N, Figel SA, Wilson KE, Morrison CD, Gelman IH et al. PTPN14 interacts with and negatively regulates oncogenic function of YAP. Oncogene 2013; 32: 1266–1273.

    Article  Google Scholar 

  3. 3

    Gaffney CJ, Oka T, Mazack V, Hilman D, Gat U, Muramatsu T et al. Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene. Gene 2012; 509: 215–222.

    CAS  Article  Google Scholar 

  4. 4

    Oka T, Schmitt AP, Sudol M . Opposing roles of angiomotin-like-1 and zona occludens-2 on pro-apoptotic function of YAP. Oncogene 2012; 31: 128–134.

    CAS  Article  Google Scholar 

  5. 5

    Ehsanian R, Brown M, Lu H, Yang X, Pattatheyil A, Yan B et al. YAP dysregulation by phosphorylation or deltaNp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer subsets. Oncogene 2010; 29: 6160–6171.

    CAS  Article  Google Scholar 

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Acknowledgements

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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