Krishnan, Ramesh K., Nolte, Hendrik, Sun, Tianliang ORCID: 0000-0003-2407-5747, Kaur, Harmandeep, Sreenivasan, Krishnamoorthy, Looso, Mario ORCID: 0000-0003-1495-9530, Offermanns, Stefan ORCID: 0000-0001-8676-6805, Krueger, Marcus and Swiercz, Jakub M. (2015). Quantitative analysis of the TNF-alpha-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKK beta substrate. Nat. Commun., 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

The inhibitor of the nuclear factor-kappa B (I kappa B) kinase (IKK) complex is a key regulator of the canonical NF-kappa B signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-kappa B activation; however, there is increasing evidence for NF-kappa B pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-alpha-IKK beta-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which similar to 1% are regulated up on TNF-alpha stimulation. We identify various potential novel IKK beta substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKK beta on serine 298. We provide evidence that IKK beta-mediated AEG-1 phosphorylation is essential for I kappa B alpha degradation as well as NF-kappa B-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Krishnan, Ramesh K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, TianliangUNSPECIFIEDorcid.org/0000-0003-2407-5747UNSPECIFIED
Kaur, HarmandeepUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sreenivasan, KrishnamoorthyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Looso, MarioUNSPECIFIEDorcid.org/0000-0003-1495-9530UNSPECIFIED
Offermanns, StefanUNSPECIFIEDorcid.org/0000-0001-8676-6805UNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swiercz, Jakub M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-409244
DOI: 10.1038/ncomms7658
Journal or Publication Title: Nat. Commun.
Volume: 6
Date: 2015
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; ASTROCYTE ELEVATED GENE-1; SQUAMOUS-CELL CARCINOMA; IN-DEPTH ANALYSIS; TRANSCRIPTION FACTOR; TUMOR PROGRESSION; OVARIAN-CANCER; EXPRESSION; ACTIVATION; METADHERINMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/40924

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