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

Germana B Rona1, Diego S G Almeida1, Anderson S Pinheiro1

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

Oncotarget
|September 15, 2017
PubMed

Insights

The NSD3 oncogene

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • WHSC1L1/NSD3 is a potent human oncogene with two isoforms.
  • Overexpression of either NSD3 isoform can induce cancer cell transformation.
  • The short NSD3 isoform (NSD3s) possesses a PWWP domain crucial for epigenetic regulation.

Purpose of the Study:

  • To investigate the role of the NSD3s PWWP domain in tumorigenesis.
  • To utilize Saccharomyces cerevisiae as a model organism for studying NSD3 function.
  • To understand the functional conservation of PWWP domains in metabolism.

Main Methods:

  • Comparative analysis of human NSD3s and yeast Pdp3 PWWP domains.
  • Functional assays in Saccharomyces cerevisiae.
  • Domain swapping experiments between NSD3s and Pdp3.

Main Results:

  • Identified yeast Pdp3 protein with a PWWP domain similar to human NSD3s.
  • Demonstrated conserved roles of Pdp3 and NSD3s in energy metabolism, promoting fermentation.
  • Confirmed functional substitution of yeast Pdp3's PWWP domain by human NSD3s' PWWP domain.
  • Identified W21 in yeast Pdp3's PWWP domain as essential for its metabolic function.

Conclusions:

  • The PWWP domain of NSD3 plays a conserved role in metabolic regulation relevant to tumorigenesis.
  • Yeast Pdp3 serves as a functional model for studying NSD3 PWWP domain activity.
  • Specific residues within the PWWP domain are critical for its metabolic function.

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.7K
Microbial Fermentation01:23

Microbial Fermentation

Fermentation is a crucial anaerobic metabolic process that enables microbes to derive energy from sugar without relying on oxygen or an electron transport chain. This process is fundamental to various biological and industrial applications and is classified based on the metabolic products generated.Role of Pyruvate in FermentationPyruvate and its derivatives serve as key electron acceptors in fermentative pathways. The oxidation of NADH to regenerate NAD+ is essential for the continuation of...
1.6K
Other Glycolytic Pathways01:24

Other Glycolytic Pathways

The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
1.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.7K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.2K