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CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer

Title
CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer
Author
윤채옥
Keywords
CHRONIC KIDNEY-DISEASE; HEAT-SHOCK PROTEINS; TISSUE TRANSGLUTAMINASE; CELL CARCINOMA; BREAST-CANCER; PROTEASOMAL DEGRADATION; E3 LIGASE; PROGNOSTIC-SIGNIFICANCE; CROSS-LINKING; EXPRESSION
Issue Date
2015-11
Publisher
NATURE PUBLISHING GROUP
Citation
ONCOGENE, v.35, NO 28, Page. 3718-3728
Abstract
The multifunctional enzyme transglutaminase 2 (TG2) primarily catalyzes cross-linking reactions of proteins via (γ-glutamyl) lysine bonds. Several recent findings indicate that altered regulation of intracellular TG2 levels affects renal cancer. Elevated TG2 expression is observed in renal cancer. However, the molecular mechanism underlying TG2 degradation is not completely understood. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase. Previous studies reveal that CHIP deficiency mice displayed a reduced life span with accelerated aging in kidney tissues. Here we show that CHIP promotes polyubiquitination of TG2 and its subsequent proteasomal degradation. In addition, TG2 upregulation contributes to enhanced kidney tumorigenesis. Furthermore, CHIP-mediated TG2 downregulation is critical for the suppression of kidney tumor growth and angiogenesis. Notably, our findings are further supported by decreased CHIP expression in human renal cancer tissues and renal cancer cells. The present work reveals that CHIP-mediated TG2 ubiquitination and proteasomal degradation represent a novel regulatory mechanism that controls intracellular TG2 levels. Alterations in this pathway result in TG2 hyperexpression and consequently contribute to renal cancer.
URI
http://www.nature.com/onc/journal/v35/n28/full/onc2015439a.html?foxtrotcallback=truehttp://hdl.handle.net/20.500.11754/28804
ISSN
0950-9232; 1476-5594
DOI
10.1038/onc.2015.439
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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