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

B. Min, H. Park, S. Lee, Y. Li, J. M. Choi, J. Y. Lee, J. Kim, Youngdeuk Choi, Young-Guen Kwon, H. W. Lee, S. C. Bae, C. O. Yun, Kwang Chul Chung

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3718-3728
Number of pages11
JournalOncogene
Volume35
Issue number28
DOIs
Publication statusPublished - 2016 Jul 14

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Kidney Neoplasms
Proteolysis
Growth
Neoplasms
Proteins
Kidney
Multifunctional Enzymes
transglutaminase 2
Protein Deficiency
Ubiquitin-Protein Ligases
Ubiquitination
Cross Reactions
Renal Cell Carcinoma
Lysine
Carcinogenesis
Up-Regulation
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Min, B. ; Park, H. ; Lee, S. ; Li, Y. ; Choi, J. M. ; Lee, J. Y. ; Kim, J. ; Choi, Youngdeuk ; Kwon, Young-Guen ; Lee, H. W. ; Bae, S. C. ; Yun, C. O. ; Chung, Kwang Chul. / CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer. In: Oncogene. 2016 ; Vol. 35, No. 28. pp. 3718-3728.
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Min, B, Park, H, Lee, S, Li, Y, Choi, JM, Lee, JY, Kim, J, Choi, Y, Kwon, Y-G, Lee, HW, Bae, SC, Yun, CO & Chung, KC 2016, 'CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer', Oncogene, vol. 35, no. 28, pp. 3718-3728. https://doi.org/10.1038/onc.2015.439

CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer. / Min, B.; Park, H.; Lee, S.; Li, Y.; Choi, J. M.; Lee, J. Y.; Kim, J.; Choi, Youngdeuk; Kwon, Young-Guen; Lee, H. W.; Bae, S. C.; Yun, C. O.; Chung, Kwang Chul.

In: Oncogene, Vol. 35, No. 28, 14.07.2016, p. 3718-3728.

Research output: Contribution to journalArticle

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