The sentence you wrote is this "However, with regard to oncogenes, the research suggests it isn't the function of the protein product that is necessarily altered in an oncogenic mutation, but rather a change in transcription regulation"
You say in this sentence that it isn't the function of the protein but transcription regulation. Do changes in transcription cause cancer? Yes. Do changes in protein function cause cancer? Yes. Your statement is wrong then or very missleading. Gleevec one of the most successful cancer drugs targets protein function!
All protein function can indirectly or convolutedly be related to gene regulation but I don't think that is what you were tryign to say.
Scott, what you quote from Wikipedia:
"The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation: A mutation within a proto-oncogene, or within a regulatory region (for example the promoter region), can cause a change in the protein structure, causing
- an increase in protein (enzyme) activity"
The paper title you cite, Inefficient ubiquitination is protein function...
None of that has anything to do with transcription.
"Receptor Tyrosine Kinases add phosphate groups to other proteins to turn them on or off. Receptor kinases add phosphate groups to receptor proteins at the surface of the cell (which receive protein signals from outside the cell and transmit them to the inside of the cell). Tyrosine kinases add phosphate groups to the amino acid tyrosine in the target protein. They can cause cancer by turning the receptor permanently on (constitutively), even without signals from outside the cell."
Constitutively turning a protein on is a change in protein function not transcription regulation.
Glad to hear Sigma wants to produce your Zinc-finger configuration pro-bono. You should go with that.
You should send your paper off for peer-reviewed publication. I see you have a similar "paper" "published" in the journal of "Technological Innovations in Life Sciences", which has published 6 articles 3 of which are written by the Editor and maybe 3 of which are actual papers in its 5 year history. None of its articles have ever been cited and none of its articles have ever been written by Academic Faculty. Sounds a bit sketchy...
Send your article to PLoS One. They have an option that allows you to wave the publication costs.
Sorry you had to spend so much money for Scientific articles. If you search this list there are many ways to obtain them for free, including going to the library at your local university.
I look forward to hearing your response to my critiques.
Hello,
First, my thanks for taking the time to review and comment. I actually wasn't looking for a critique, but rather someone to work with me to develop and execute assays. Sigma Aldrich may be willing to produce my zinc-finger configuration pro bono… I've already been invited up to the Institute for Advanced Biotechnology and Medicine to discuss my paper, and I've conversed with Dr. June and Dr. Wender (Bergstrom Professor of Chemistry, Stanford) among others about my proposed therapeutic and none expressed any concerns regarding neither the fundamentals nor feasibility of the approach I put forth.
I am surprised that you came to the conclusion that my proposed therapeutic involves a T Cell... it does not, it is a single chimeric protein having nothing to do with any lymphocyte… my apologies if my writing wasn't clear.
Also, again, although I appreciate your time, I take offense at your inferring that I simply read abstracts; I assure you I read several hundred pages (and a textbook or two) of research over several months and incurred a large expense acquiring those papers despite the fact that my tax dollars paid for much of the research.
I also disagree with (though appreciate :) ) just about every one of your assertions. I'll address the rest tomorrow, but just for starters… Take the Oncogenes... I wrote "but rather a change in transcription regulation, a substantial decrease in the ubiquitination-proteasome turnover rate, or its active state changing from induced to constitutive that is the actual driver of oncogenesis (8) (9). "
Each of those three assertions are accurate reflections of those made in the research I cited. In fact you wouldn't even have to read passed the title of the papers… referring to c-Myc; "hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover"
even the Wiki article you linked states:
"an increase in protein (enzyme) activity… and a loss of regulation" and all but 3.2 specifically refer to regulation, not a change in primary function and even 3.2 refers to a change in state to constitutively active…
Thanks again,
Scott
On Monday, July 1, 2013 4:47:47 PM UTC-4, Mackenzie Cowell wrote:Passing your message on to the main list, Scott.---------- Forwarded message ----------
From: Scott Tarone <sta...@synapticsynthase.com>
Date: Sun, Jun 30, 2013 at 7:16 PM
Subject: Intein control in a targeted cancer therapy
To: con...@diybio.orgHello,
I'm not sure if your group is the right place for me to look for help, but I thought it worth a shot.
I am self-taught in the biosciences… Neuroscience, Genetics, Immunology, and Targeted Cancer Therapies. After watching a presentation on Chimeric Antigen Receptors on the NIH site, I had an idea on another approach that would remove the limitations inherent in the technique presented (though it was a fantastic step forward, and very successful). My approach is based on a constitutively active Caspase 3 mutant controlled by a molecular switch.
Long story short… I just wrote up a few paragraphs on my idea and sent it off to a few people in the field. One of them (a senior scientist from Pfizer) got back to me a few months later and said I may be on to something and that I needed to write a paper. I did that and then wrote an article on that paper with him and that was published in a small time online journal last year. Since then my paper and the article have been download several hundred times.
I didn't provide the links or an attachment as my first attempt to send this email was blocked by spam filters.. I will provide that information if you have interest. In the interim, you can search for "intracellular Caspase modulating Chimeric Antigen Receptor".
Thank you very much for your time…
Take care,
Scott
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