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Plos One : the Tbc1D15 Oncoprotein Controls Stem Cell Self- Renewal Through Destabilization of the Numb-p53 Complex, Volume 8

By Bartosch, Birke

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Book Id: WPLBN0003968553
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : the Tbc1D15 Oncoprotein Controls Stem Cell Self- Renewal Through Destabilization of the Numb-p53 Complex, Volume 8  
Author: Bartosch, Birke
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
Publication Date:
Publisher: Plos

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Bartosch, B. (n.d.). Plos One : the Tbc1D15 Oncoprotein Controls Stem Cell Self- Renewal Through Destabilization of the Numb-p53 Complex, Volume 8. Retrieved from http://worldebookfair.com/


Description
Description : Stem cell populations are maintained through self-renewing divisions in which one daughter cell commits to a specific fate while the other retains the multipotent characteristics of its parent. The p53 tumor suppressor, in conjunction with its interacting partner protein Numb, preserves this asymmetry and functions as a vital barrier against the unchecked expansion of tumor stem cell pools: however, little is known about the biological control of the Numb-p53 interaction. We show here that Numb and p53 are the constituents of a high molecular mass complex, which is disintegrated upon activation of aPKCf, a Numb kinase. Using large-scale affinity purification and tandem mass spectrometry, we identify TBC1D15 as a Numb-associated protein and demonstrate that its amino-terminal domain disengages p53 from Numb, triggering p53 proteolysis and promoting self-renewal and pluripotency. Cellular levels of TBC1D15 are diminished upon acute nutrient deprivation through autophagy-mediated degradation, indicating that TBC1D15 serves as a conduit through which cellular metabolic status is linked to self-renewal. The profound deregulation of TBC1D15 expression exhibited in a diverse array of patient tumors underscores its proposed function as an oncoprotein.

 

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