WWP1-dependent ubiquitination and degradation of the lung Krüppel-like factor, KLF2

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• 作者：Zhang ; Xiaoling ; Srinivasan ; Seetha V. ; Lingrel ; Jerry B.
• 关键词：Lung Krü ; ppel-like factor ; KLF2 ; E3-ubiquitin ligase ; WWP1 ; Ubiquitination ; Post-translational modification of Krü ; ppel-like factors
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：March 26, 2004
• 年：2004
• 卷：316
• 期：1
• 页码：139-148
• 全文大小：3.75 M

文摘

The zinc-finger transcription factor Krüppel-like factor-2 plays an important role in pulmonary development, inhibition of adipocyte differentiation, and maintaining quiescence in single-positive T cells. KLF2 levels rapidly decrease during adipogenesis and activation of T cells, but the pathways involved remain unclear. Previously, we identified WWP1, a HECT-domain E3-ubiquitin ligase, as an interacting partner of KLF2. This led us to speculate that KLF2 may be targeted for ubiquitination. Here, we demonstrate that WWP1 interacts with KLF2 in vivo and mediates both poly-ubiquitination and proteasomal degradation of KLF2. Deleting the inhibitory domain of KLF2 abrogated KLF2–WWP1 interactions and abolished WWP1-mediated poly-ubiquitination and down-regulation of KLF2. Furthermore, lysine-121 in the inhibitory domain of KLF2 is critical for ubiquitin-conjugation. Finally, the catalytic cysteine of WWP1 is not required for KLF2-ubiquitination. Our experiments demonstrate for the first time that WWP1 promotes ubiquitination and degradation of KLF2 and is not involved in the ubiquitin-transfer reaction.