Universität zu Köln

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 ORCID: 0000-0003-2008-4582 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:	Creators Email ORCID ORCID Put Code Krishnan, Ramesh K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Sun, Tianliang UNSPECIFIED orcid.org/0000-0003-2407-5747 UNSPECIFIED Kaur, Harmandeep UNSPECIFIED UNSPECIFIED UNSPECIFIED Sreenivasan, Krishnamoorthy UNSPECIFIED UNSPECIFIED UNSPECIFIED Looso, Mario UNSPECIFIED orcid.org/0000-0003-1495-9530 UNSPECIFIED Offermanns, Stefan UNSPECIFIED orcid.org/0000-0001-8676-6805 UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Swiercz, Jakub M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; ASTROCYTE ELEVATED GENE-1; SQUAMOUS-CELL CARCINOMA; IN-DEPTH ANALYSIS; TRANSCRIPTION FACTOR; TUMOR PROGRESSION; OVARIAN-CANCER; EXPRESSION; ACTIVATION; METADHERIN Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/40924