Affinity purification-mass spectrometry analysis of bcl-2 interactome identified SLIRP as a novel interacting protein

Members of the bcl-2 protein family share regions of sequence similarity, the bcl-2 homology (BH) domains. Bcl-2, the most studied member of this family, has four BH domains, BH1–4, and has a critical role in resistance to antineoplastic drugs by regulating the mitochondrial apoptotic pathway. Moreo...

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Bibliographic Details
Published in:	Cell death & disease Vol. 7; no. 2; p. e2090
Main Authors:	Trisciuoglio, D, Desideri, M, Farini, V, De Luca, T, Di Martile, M, Tupone, M G, Urbani, A, D'Aguanno, S, Del Bufalo, D
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 11-02-2016 Springer Nature B.V Nature Publishing Group
Subjects:	13/1 13/2 13/31 13/89 14/63 45/77 631/45/475/2290 631/67 631/80/82/23 82/58 Analysis Antibodies Apoptosis - physiology Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Drug resistance Humans Immunology Life Sciences Mass Spectrometry - methods Original original-article Proteins Proto-Oncogene Proteins c-bcl-2 - metabolism Reactive Oxygen Species - metabolism Ribonucleic acid RNA RNA-Binding Proteins - genetics RNA-Binding Proteins - isolation & purification RNA-Binding Proteins - metabolism Studies
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Summary:	Members of the bcl-2 protein family share regions of sequence similarity, the bcl-2 homology (BH) domains. Bcl-2, the most studied member of this family, has four BH domains, BH1–4, and has a critical role in resistance to antineoplastic drugs by regulating the mitochondrial apoptotic pathway. Moreover, it is also involved in other relevant cellular processes such as tumor progression, angiogenesis and autophagy. Deciphering the network of bcl-2-interacting factors should provide a critical advance in understanding the different functions of bcl-2. Here, we characterized bcl-2 interactome by mass spectrometry in human lung adenocarcinoma cells. In silico functional analysis associated most part of the identified proteins to mitochondrial functions. Among them we identified SRA stem–loop interacting RNA-binding protein, SLIRP, a mitochondrial protein with a relevant role in regulating mitochondrial messenger RNA (mRNA) homeostasis. We validated bcl-2/SLIRP interaction by immunoprecipitation and immunofluorescence experiments in cancer cell lines from different histotypes. We showed that, although SLIRP is not involved in mediating bcl-2 ability to protect from apoptosis and oxidative damage, bcl-2 binds and stabilizes SLIRP protein and regulates mitochondrial mRNA levels. Moreover, we demonstrated that the BH4 domain of bcl-2 has a role in maintaining this binding.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work and should be considered as equal last authors.
ISSN:	2041-4889 2041-4889
DOI:	10.1038/cddis.2015.357