0 92

Cited 5 times in

TPT1 (tumor protein, translationally-controlled 1) negatively regulates autophagy through the BECN1 interactome and an MTORC1-mediated pathway

Authors
 Seong-Yeon Bae  ;  Sanguine Byun  ;  Soo Han Bae  ;  Do Sik Min  ;  Hyun Ae Woo  ;  Kyunglim Lee 
Citation
 Autophagy, Vol.13(5) : 820-833, 2017 
Journal Title
 Autophagy 
ISSN
 1554-8627 
Issue Date
2017
MeSH
Animals ; Autophagy/physiology* ; Beclin-1/metabolism* ; Biomarkers, Tumor/metabolism* ; Gene Knockdown Techniques/methods ; Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mice ; Neoplasm Proteins/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Processing, Post-Translational/physiology ; Signal Transduction
Keywords
BCL2 ; BECN1 ; MTORC1 ; TP53 target gene ; TPT1/TCTP ; autophagy
Abstract
TPT1/TCTP (tumor protein, translationally-controlled 1) is highly expressed in tumor cells, known to participate in various cellular activities including protein synthesis, growth and cell survival. In addition, TPT1 was identified as a direct target of the tumor suppressor TP53/p53 although little is known about the mechanism underlying the anti-survival function of TPT1. Here, we describe a role of TPT1 in the regulation of the MTORC1 pathway through modulating the molecular machinery of macroautophagy/autophagy. TPT1 inhibition induced cellular autophagy via the MTORC1 and AMPK pathways, which are inhibited and activated, respectively, during treatment with the MTOR inhibitor rapamycin. We also found that the depletion of TPT1 potentiated rapamycin-induced autophagy by synergizing with MTORC1 inhibition. We further demonstrated that TPT1 knockdown altered the BECN1 interactome, a representative MTOR-independent pathway, to stimulate autophagosome formation, via downregulating BCL2 expression through activating MAPK8/JNK1, and thereby enhancing BECN1-phosphatidylinositol 3-kinase (PtdIns3K)-UVRAG complex formation. Furthermore, reduced TPT1 promoted autophagic flux by modulating not only early steps of autophagy but also autophagosome maturation. Consistent with in vitro findings, in vivo organ analysis using Tpt1 heterozygote knockout mice showed that autophagy is enhanced because of haploinsufficient TPT1 expression. Overall, our study demonstrated the novel role of TPT1 as a negative regulator of autophagy that may have potential use in manipulating various diseases associated with autophagic dysfunction.
Full Text
http://www.tandfonline.com/doi/full/10.1080/15548627.2017.1287650
DOI
10.1080/15548627.2017.1287650
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
배수한(Bae, Soo Han) ORCID logo https://orcid.org/0000-0002-8007-2906
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154238
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse