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New interactions uncovered affecting TGF-beta pathway in humans

Date:
December 21, 2015
Source:
National University of Singapore
Summary:
The USP15 protein has been identified as novel target for therapy against cancer progression, investigators report. In certain settings, the TGF-beta pathway can act as an oncogene, enhancing cancer progression in humans.
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Molecular model showing the novel proposed mechanism for the activation of SMURF2. The C-lobe (in yellow) of the SMURF2 protein interacts with an ubiquitin molecule (in green), which was transferred to SMURF2 by USP15.
Credit: Image courtesy of National University of Singapore

Researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) have delineated novel molecular interactions affecting the activity of the TGF-β pathway, a key cancer pathway in humans affecting cancer progression.

In certain settings, the TGF-β pathway can act as an oncogene, enhancing cancer progression in humans. The activation of this pathway can increase the growth of tumors by promoting cell invasion, activating cancer stem cells, and in some cases, promoting the spread of cancer. In recent years, a number of deubiquitinating enzymes have been shown to regulate the TGF-β pathway and may potentially be considered as a new class of drug targets. Studies have shown that the deubiquitinating enzyme USP15 is elevated in glioblastoma, a highly invasive tumor in the brain, as well as breast and ovarian cancers, leading to the over-activation of the TGF-β pathway and increasing cancer risks.

A recent study conducted by Dr Pieter Eichhorn and Dr Prasanna Iyengar from CSI Singapore revealed that the activation of the TGF-β pathway could be influenced by the interactions between USP15 and SMURF2 -- enzymes generally involved in degradation of proteins in cells.

"While existing studies have found a number of deubiquitinating enzymes that stabilise the TGF-β receptor, leading to the activation of the TGF-β pathway, the mechanism has not been well studied. Our research found that USP15 could regulate the ability of SMURF2 to add ubiquitin molecules to its targets, resulting in enhanced stability of the TGF-β receptor and downstream pathway activation. Hence, the results of this study point to USP15 as a potential novel therapeutic target for the treatment of cancers with TGF-β hyperactivation," said Dr Eichhorn.

The findings of the research study were published online in Scientific Reports, a journal by Nature Publishing Group, in October 2015.


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Materials provided by National University of Singapore. Note: Content may be edited for style and length.


Journal Reference:

  1. Prasanna Vasudevan Iyengar, Patrick Jaynes, Laura Rodon, Dilraj Lama, Kai Pong Law, Yoon Pin Lim, Chandra Verma, Joan Seoane, Pieter Johan Adam Eichhorn. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Scientific Reports, 2015; 5: 14733 DOI: 10.1038/srep14733

Cite This Page:

National University of Singapore. "New interactions uncovered affecting TGF-beta pathway in humans." ScienceDaily. ScienceDaily, 21 December 2015. <www.sciencedaily.com/releases/2015/12/151221071627.htm>.
National University of Singapore. (2015, December 21). New interactions uncovered affecting TGF-beta pathway in humans. ScienceDaily. Retrieved May 28, 2017 from www.sciencedaily.com/releases/2015/12/151221071627.htm
National University of Singapore. "New interactions uncovered affecting TGF-beta pathway in humans." ScienceDaily. www.sciencedaily.com/releases/2015/12/151221071627.htm (accessed May 28, 2017).

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