Navigation Links
Protein improves efficacy of tumor-killing enzyme

Scientists have devised a method for delivering tumor cell-killing enzymes in a way that protects the enzyme until it can do its work inside the cell. In their study in mBio, the online open-access journal of the American Society for Microbiology, researchers assembled microscopic protein packages that can deliver an enzyme called PEIII to the insides of cells. By attaching a protein called ubiquitin to the enzyme, they were able to protect it from degradation by the cell, allowing the enzyme to complete its mission. The results indicate that ubiquitin may be a useful addition to targeted toxins.

Although researchers have been developing tumor-directed "targeted toxins" for decades, their success has been hindered by technical problems, including inadequate tumor specificity, low efficiency of delivery to the interior of the cell (also called the cytosol), and other issues. In this study, researchers from the National Institute of Allergy and Infectious Diseases sought to improve the persistence of the enzyme in the cytosol.

They created bundles of proteins designed to carry this out. The targeted toxin assembly included two components the researchers have used before in targeted toxins: the "killing" enzyme PEIII, and a set of targeting proteins called LFn that deliver the PEIII enzyme via pores to the inside of the cell. The LFn delivery system was engineered to specifically target and attach to tumor cells.

The third component in the bundle was a new addition: ubiquitin, a small protein that is normally used by cells to target waste proteins for degradation. The researchers inserted ubiquitin in between the LFn and the PEIII, then tested the bundle on mice with tumors. The idea was to use the cell's own ubiquitin-cleaving enzymes to cut the ubiquitin off and free up the PEIII enzyme once it's inside the cell.

The system worked. Tumor growth was inhibited in mice treated with targeted toxins that either carried the wild-type ubiquitin or engineered ubiquitin without lysine residues in it, a change that should prevent it from being degraded by the cell. The addition of ubiquitin enhanced the ability of the PEIII enzyme to persist inside the cell thereby enhancing its potency. And the ubiquitin didn't seem to hinder the efficiency of delivering the PEIII inside the cell.

As an added bonus, the addition of ubiquitin reduced the toxicity of the targeted toxin to non-tumor tissues.

The authors point out that the use of ubiquitin linkers shows considerable promise and could be an effective strategy for enhancing the potency of tumor-targeting toxins for use in patients. In research currently underway, they are attempting to improve on the system by making changes to the ubiquitin that allow it to unfold appropriately inside the cell.


Contact: Jim Sliwa
American Society for Microbiology

Related biology news :

1. Rare, lethal childhood disease tracked to protein
2. National survey highlights perceived importance of dietary protein to prevent weight gain
3. Scientists discover new way protein degradation is regulated
4. Science surprise: Toxic protein made in unusual way may explain brain disorder
5. Metabolic fingerprinting: Using proteomics to identify proteins in gymnosperm pollination drops
6. AACR news: Six2 homeoprotein allows breast cancer cells to detach and metastasize
7. A proteins well-known cousin sheds light on its gout-linked relative
8. Mechanism of mutant histone protein in childhood brain cancer revealed
9. Pitt team finds immunity protein that ramps up inflammation, and agents that can block it
10. Market Analysis: Biomaterials and Engineered Protein
11. Transmission routes of spreading protein particles
Post Your Comments:
(Date:11/17/2015)... Paris from 17 th until ... from 17 th until 19 th November ... has invented the first combined scanner in the world which scans ... Until now two different scanners were required: one for passports ... on the same surface. This innovation is an ideal solution ...
(Date:11/17/2015)... 2015  Vigilant Solutions announces today that Mr. ... Directors. --> --> ... the partnership at TPG Capital, one of the largest ... Billion in revenue.  He founded and led TPG,s Operating ... companies, from 1997 to 2013.  In his first role, ...
(Date:11/16/2015)... Nov 16, 2015  Synaptics Inc. (NASDAQ: ... solutions, today announced expansion of its TDDI product ... touch controller and display driver integration (TDDI) solutions ... These new TDDI products add to the previously-announced ... TD4302 (WQHD resolution), and TD4322 (FHD resolution) solutions. ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ... November 25, 2015 , ... Jessica Richman and ... early in their initial angel funding process. Now, they are paying it forward ... make early stage investments in the microbiome space. In this, they join ...
(Date:11/24/2015)... Nov. 24, 2015 Cepheid (NASDAQ: CPHD ... at the following conference, and invited investors to participate ...      Tuesday, December 1, 2015 at 11.00 a.m. ...      Tuesday, December 1, 2015 at 11.00 a.m. ... New York, NY      Tuesday, December ...
(Date:11/24/2015)... , ... November 24, 2015 , ... ... healthy metabolism. But unless it is bound to proteins, copper is also toxic ... (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a systematic study of ...
(Date:11/24/2015)... , Nov. 24, 2015  Clintrax Global, Inc., a worldwide ... Carolina , today announced that the company has set a ... a 391% quarter on quarter growth posted for Q3 of 2014 ... and Mexico , with the establishment of ... December 2015. --> United Kingdom and ...
Breaking Biology Technology: