| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 64786 |
Name | TBC1D15 |
Synonymous | TBC1 domain family, member 15;TBC1D15;TBC1 domain family, member 15 |
Definition | GAP for RAB7|GTPase-activating protein RAB7|TBC1 domain family member 15|Tre-2-budding uninhibited by benzimidazole-cell division cycle 16 domain, domain family member 15|Tre2/Bub2/Cdc16 domain family member 15 |
Position | 12q21.1 |
Gene type | protein-coding |
Title | Abstract |
| The TBC1D15 oncoprotein controls stem cell self-renewal through destabilization of the Numb-p53 complex. | 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 aPKCzeta, 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. |