Enhancer of rudimentary homologue interacts with scaffold attachment factor B at the nuclear matrix to regulate SR protein phosphorylation. (8th July 2017)

• Record Type: Journal Article
• Authors: Drakouli, Sotiria; Lyberopoulou, Aggeliki; Papathanassiou, Maria; Mylonis, Ilias; Georgatsou, Eleni
• Is Part Of: FEBS journal. Volume 284:Number 15(2017)
• Page Start: 2482
• Page End: 2500
• Publication Date: 2017-07-08
• Subjects: ERH -- nuclear matrix -- SAFB -- SR protein -- SRPK1; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14141
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Scaffold attachment factor B1 (SAFB1) is an integral component of the nuclear matrix of vertebrate cells. It binds to DNA on scaffold/matrix attachment region elements, as well as to RNA and a multitude of different proteins, affecting basic cellular activities such as transcription, splicing and DNA damage repair. In the present study, we show that enhancer of rudimentary homologue (ERH) is a new molecular partner of SAFB1 and its 70% homologous paralogue, scaffold attachment factor B2 (SAFB2). ERH interacts directly in the nucleus with the C‐terminal Arg‐Gly‐rich region of SAFB1/2 and co‐localizes with it in the insoluble nuclear fraction. ERH, a small ubiquitous protein with striking homology among species and a unique structure, has also been implicated in fundamental cellular mechanisms. Our functional analyses suggest that the SAFB/ERH interaction does not affect SAFB1/2 function in transcription (e.g. as oestrogen receptor α co‐repressors), although it reverses the inhibition exerted by SAFB1/2 on the splicing kinase SR protein kinase 1 (SRPK1), which also binds on the C‐terminus of SAFB1/2. Accordingly, ERH silencing decreases lamin B receptor and SR protein phosphorylation, which are major SRPK1 substrates, further substantiating the role of SAFB1 and SAFB2 in the co‐ordination of nuclear function. Abstract : The R/G rich C‐terminal domain of scaffold attachment factor‐B (SAFB)1/2 was found to directly interact with enhancer of rudimentary homologue (ERH). When the ERH concentration is high, SAFBs and ERH form a complex. As a result, SAFB does not exert its inhibitory effect on SR protein kinase 1 (SRPK1) and SR‐proteins are phosphorylated. Conversely, when ERH is low, SAFBs inhibit SRPK1 function inside the nucleus.