W. Rathmell
Last active: 8/8/2016

Regulation of KLF4 turnover reveals an unexpected tissue-specific role of pVHL in tumorigenesis.

Gamper AM, Qiao X, Kim J, Zhang L, DeSimone MC, Rathmell WK, Wan Y
Mol Cell. 2012 45 (2): 233-43

PMID: 22284679 · PMCID: PMC3982234 · DOI:10.1016/j.molcel.2011.11.031

The transcription factor Krüppel-like factor 4 (KLF4) is an important regulator of cell-fate decision, including cell-cycle regulation, apoptosis, and stem cell renewal, and plays an ambivalent role in tumorigenesis as a tissue-specific tumor suppressor or oncogene. Here, we report that the Von Hippel-Lindau gene product, pVHL, physically interacts with KLF4 and regulates its rapid turnover observed in both differentiated and stem cells. We provide mechanistic insights into KLF4 degradation and show that pVHL depletion in colorectal cancer cells leads to cell-cycle arrest concomitant with increased transcription of the KLF4-dependent p21 gene. Finally, immunohistochemical staining revealed elevated pVHL and reduced KLF4 levels in colon cancer tissues. We therefore propose that unexpectedly pVHL, via the degradation of KLF4, is a facilitating factor in colorectal tumorigenesis.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (10)

Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic Colorectal Neoplasms Cyclin-Dependent Kinase Inhibitor p21 Half-Life HeLa Cells Humans Kruppel-Like Transcription Factors Von Hippel-Lindau Tumor Suppressor Protein

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