NEDD4-induced degradative ubiquitination of phosphatidylinositol 4-phosphate 5-kinase α and its implication in breast cancer cell proliferation

Journal of Cellular and Molecular Medicine
Mai Hoang TranSang Yoon Lee

Abstract

Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members generate phosphatidylinositol 4,5-bisphosphate (PIP2), a critical lipid regulator of diverse physiological processes. The PIP5K-dependent PIP2 generation can also act upstream of the oncogenic phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Many studies have demonstrated various mechanisms of spatiotemporal regulation of PIP5K catalytic activity. However, there are few studies on regulation of PIP5K protein stability. Here, we examined potential regulation of PIP5Kα, a PIP5K isoform, via ubiquitin-proteasome system, and its implication for breast cancer. Our results showed that the ubiquitin ligase NEDD4 (neural precursor cell expressed, developmentally down-regulated gene 4) mediated ubiquitination and proteasomal degradation of PIP5Kα, consequently reducing plasma membrane PIP2 level. NEDD4 interacted with the C-terminal region and ubiquitinated the N-terminal lysine 88 in PIP5Kα. In addition, PIP5Kα gene disruption inhibited epidermal growth factor (EGF)-induced Akt activation and caused significant proliferation defect in breast cancer cells. Notably, PIP5Kα K88R mutant that was resistant to NEDD4-mediated ubiquitination and degradation showed more potentiat...Continue Reading

References

Jan 5, 2000·The EMBO Journal·J S ThrowerC M Pickart
May 26, 2001·Science·S SantagataL Shapiro
Oct 13, 2006·Nature·Gilbert Di Paolo, Pietro De Camilli
Jan 16, 2007·Cell·Xinjiang WangXuejun Jiang
May 24, 2007·Pflügers Archiv : European journal of physiology·Yuntao S Mao, Helen L Yin
May 31, 2007·Breast Cancer Research : BCR·Vincent VuaroqueauxSerenella Eppenberger-Castori
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Jun 20, 2008·Proceedings of the National Academy of Sciences of the United States of America·Fatemeh FouladkouDaniela Rotin
Jul 5, 2008·Cancer Cell·Francesca BernassolaGerry Melino
Oct 22, 2008·Methods : a Companion to Methods in Enzymology·Péter Várnai, Tamas Balla
Feb 7, 2009·Physiology·Heather J McCrea, Pietro De Camilli
May 14, 2009·Nature Reviews. Molecular Cell Biology·Daniela Rotin, Sharad Kumar
Nov 6, 2009·Journal of Cell Science·Iman van den Bout, Nullin Divecha
Dec 3, 2009·Molecular Systems Biology·Avinash PersaudDaniela Rotin
Jan 21, 2010·Physiological Reviews·Juha SaarikangasPekka Lappalainen
Jun 19, 2010·Cellular and Molecular Life Sciences : CMLS·Katarzyna Kwiatkowska
Nov 27, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·Wentao QiSuzana D Savkovic
Jul 19, 2011·The EMBO Journal·Avinash PersaudDaniela Rotin
Sep 23, 2011·The Biochemical Journal·Harald W PlattaHarald Stenmark
Nov 24, 2012·Cell Death and Differentiation·P Y LiuT Liu
Apr 12, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Yue SunRichard A Anderson
Aug 1, 2013·Physiological Reviews·Tamas Balla
Aug 24, 2013·PloS One·Ying JiangAi-Guo Shen
Jan 21, 2014·Biochimica Et Biophysica Acta·Senena Corbalan-Garcia, Juan C Gómez-Fernández
Apr 22, 2014·Cell Reports·Taoling ZengHong-Rui Wang
Jul 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Julius SemenasJenny L Persson
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Dec 21, 2014·Gene·Natasha Anne Boase, Sharad Kumar
Jun 28, 2015·Biochimica Et Biophysica Acta·Xiao ZouMichael Blank
Oct 17, 2015·Annual Review of Medicine·Ingrid A Mayer, Carlos L Arteaga
Dec 29, 2016·The EMBO Journal·Tackhoon KimDae-Sik Lim

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Methods Mentioned

BETA
ubiquitination
PCR
gene knockout
immunoprecipitation
confocal microscopy
transfection

Software Mentioned

GraphPad Prism
NIH ImageJ

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