Research Papers:

The PWWP domain of the human oncogene WHSC1L1/NSD3 induces a metabolic shift toward fermentation

Germana B. Rona _, Diego S. G. Almeida, Anderson S. Pinheiro and Elis C. A. Eleutherio

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Oncotarget. 2017; 8:54068-54081. https://doi.org/10.18632/oncotarget.11253

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Germana B. Rona1, Diego S. G. Almeida1, Anderson S. Pinheiro1 and Elis C. A. Eleutherio1

1Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, 21941-909, Rio de Janeiro, RJ, Brazil

Correspondence to:

Germana B. Rona, email: [email protected]

Keywords: PWWP, NSD3, Pdp3, Saccharomyces cerevisiae, cancer

Received: October 29, 2015     Accepted: July 26, 2016     Published: August 12, 2016


WHSC1L1/NSD3, one of the most aggressive human oncogenes, has two isoforms derived from alternative splicing. Overexpression of long or short NSD3 is capable of transforming a healthy into a cancer cell. NSD3s, the short isoform, contains only a PWWP domain, a histone methyl-lysine reader involved in epigenetic regulation of gene expression. With the aim of understanding the NSD3s PWWP domain role in tumorigenesis, we used Saccharomyces cerevisiae as an experimental model. We identified the yeast protein Pdp3 that contains a PWWP domain that closely resembles NSD3s PWWP. Our results indicate that the yeast protein Pdp3 and human NSD3s seem to play similar roles in energy metabolism, leading to a metabolic shift toward fermentation. The swapping domain experiments suggested that the PWWP domain of NSD3s functionally substitutes that of yeast Pdp3, whose W21 is essential for its metabolic function.

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