Regulation of KLF4 Turnover Reveals an Unexpected Tissue-Specific Role of pVHL in Tumorigenesis

被引：71

作者：

Gamper, Armin M. ^{[1
,2
]}

Qiao, Xinxian ^{[1
,2
]}

Kim, Jennifer ^{[3
]}

Zhang, Liyong ^{[1
,2
]}

DeSimone, Michelle C. ^{[4
]}

Rathmell, W. Kimryn ^{[4
]}

Wan, Yong ^{[1
,2
]}

机构：

[1] Univ Pittsburgh, Dept Cell Biol & Physiol, Sch Med, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA

[3] Carnegie Mellon Univ, Dept Biol, Pittsburgh, PA 15213 USA

[4] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

来源：

MOLECULAR CELL | 2012年 / 45卷 / 02期

基金：

美国国家卫生研究院;

关键词：

KRUPPEL-LIKE FACTOR-4; HIPPEL-LINDAU-DISEASE; TUMOR-SUPPRESSOR; DNA-DAMAGE; CANCER; CELLS; KRUPPEL-LIKE-FACTOR-4; PROTEIN; GROWTH; MODELS;

D O I：

10.1016/j.molcel.2011.11.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The transcription factor Kruppel-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.

引用

页码：233 / 243

页数：11

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