Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome

Menon, Suchithra; Tsuge, Tomohiko; Dohmae, Naoshi; Takio, Koji; Ning Wei
January 2008
BMC Biochemistry;2008, Vol. 9, Special section p1
Academic Journal
Background: Cullin-RING ubiquitin E3 ligases (CRLs) are regulated by modification of an ubiquitin-like protein, Nedd8 (also known as Rub1) on the cullin subunit. Neddylation is shown to facilitate E3 complex assembly; while un-neddylated cullins are bound by CAND1 that prevents recruitment of the substrates. The level of Nedd8 modification is critically dependent on the COP9 signalosome (CSN), an eight-subunit protein complex containing Nedd8 isopeptidase activity. Results: We report isolation of SAP130 (SF3b-3) as a CSN1 interacting protein. SAP130 is homologous to DDB1, and is a component of SF3b RNA splicing complex and STAGA/TFTC transcription complexes, but its specific function within these complexes is unknown. We show that SAP130 can interact with a variety of cullin proteins. It forms tertiary complexes with fully assembled CRL E3 complexes such as SCFSkp2, Elongin B/C -Cul2- VHL and Cul4-DDB complex by binding to both N-terminal and C-terminal domain of cullins. SAP130 preferentially associates with neddylated cullins in vivo. However knock-down of CAND1 abolished this preference and increased association of SAP130 with Cul2. Furthermore, we provide evidence that CSN regulates SAP130-Cul2 interaction and SAP130-associated polyubiquitinating activity. Conclusion: SAP130 is a cullin binding protein that is likely involved in the Nedd8 pathway. The association of SAP130 with various cullin member proteins such as Cul1, Cul2 and Cul4A is modulated by CAND1 and CSN. As an established component of transcription and RNA processing complexes, we hypothesis that SAP130 may link CRL mediated ubiquitination to gene expression.


Related Articles

  • Stress-Induced Alternative Splice Forms of MDM2 and MDMX Modulate the p53-Pathway in Distinct Ways. Jacob, Aishwarya G.; Singh, Ravi K.; Comiskey Jr, Daniel F.; Rouhier, Matthew F.; Mohammad, Fuad; Bebee, Thomas W.; Chandler, Dawn S. // PLoS ONE;Aug2014, Vol. 9 Issue 8, p1 

    MDM2 and MDMX are the chief negative regulators of the tumor-suppressor protein p53 and are essential for maintaining homeostasis within the cell. In response to genotoxic stress and also in several cancer types, MDM2 and MDMX are alternatively spliced. The splice variants MDM2-ALT1 and...

  • Nuclear and unclear functions of SUMO. Seeler, Jacob-S.; Dejean, Anne // Nature Reviews Molecular Cell Biology;Sep2003, Vol. 4 Issue 9, p690 

    Post-translational modification by the ubiquitin-like SUMO protein is emerging as a defining feature of eukaryotic cells. Sumoylation has crucial roles in the regulatory challenges that face nucleate cells, including the control of nucleocytoplasmic signalling and transport and the faithful...

  • Protein neddylation: beyond cullin-RING ligases. Enchev, Radoslav I.; Schulman, Brenda A.; Peter, Matthias // Nature Reviews Molecular Cell Biology;Jan2015, Vol. 16 Issue 1, p30 

    NEDD8 (neural precursor cell expressed developmentally downregulated protein 8) is a ubiquitin-like protein that activates the largest ubiquitin E3 ligase family, the cullin-RING ligases. Many non-cullin neddylation targets have been proposed in recent years. However, overexpression of exogenous...

  • The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Puklowski, Anja; Homsi, Yahya; Keller, Debora; May, Martin; Chauhan, Sangeeta; Kossatz, Uta; Grünwald, Viktor; Kubicka, Stefan; Pich, Andreas; Manns, Michael P.; Hoffmann, Ingrid; Gönczy, Pierre; Malek, Nisar P. // Nature Cell Biology;Aug2011, Vol. 13 Issue 8, p1004 

    Deregulated centrosome duplication can result in genetic instability and contribute to tumorigenesis. Here, we show that centrosome duplication is regulated by the activity of an E3-ubiquitin ligase that employs the F-box protein FBXW5 (ref. ) as its targeting subunit. Depletion of endogenous...

  • COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3σ. Choi, H H; Gully, C; Su, C-H; Velazquez-Torres, G; Chou, P-C; Tseng, C; Zhao, R; Phan, L; Shaiken, T; Chen, J; Yeung, S C; Lee, M-H // Oncogene;12/1/2011, Vol. 30 Issue 48, p4791 

    14-3-3σ, a gene upregulated by p53 in response to DNA damage, exists as part of a positive-feedback loop, which activates p53 and is a human cancer epithelial marker downregulated in various cancer types. 14-3-3σ levels are critical for maintaining p53 activity in response to DNA damage...

  • Transcriptional Effects of E3 Ligase Atrogin-1/MAFbx on Apoptosis, Hypertrophy and Inflammation in Neonatal Rat Cardiomyocytes. Yong Zeng; Hong-Xia Wang; Shu-Bin Guo; Hui Yang; Xiang-Jun Zeng; Quan Fang; Chao-Shu Tang; Jie Du; Hui-Hua Li // PLoS ONE;Jan2013, Vol. 8 Issue 1, Special section p1 

    Atrogin-1/MAFbx is an ubiquitin E3 ligase that regulates myocardial structure and function through the ubiquitin-dependent protein modification. However, little is known about the effect of atrogin-1 activation on the gene expression changes in cardiomyocytes. Neonatal rat cardiomyocytes were...

  • Cellular Proteins and HIV-1 Rev Function. Suhasini, Modem; Reddy, Thipparthi R. // Current HIV Research;Jan2009, Vol. 7 Issue 1, p91 

    The human immunodeficiency virus (HIV-1) differentially controls viral protein expression at the level of splicing as well as nuclear export of incompletely spliced viral RNA. This process, mediated by the Rev protein, interfaces with cellular components involved in post-transcriptional gene...

  • Alternative view. McCarthy, Nicola // Nature Reviews Cancer;Apr2007, Vol. 7 Issue 4, p228 

    The article reports the studies of Adrian Krainer and colleagues to explain that deregulated splicing causes tumor formation, as in the case of deregulated transcription and translation. An overview of the influence of SR protein SFRS1 on tumor formation, and changes in the expression of...

  • Not miR-ly a splicing factor: hnRNP A1 succumbs to microRNA temptation. Nielsen, Anne Færch; Leuschner, Philipp J. F.; Martinez, Javier // Nature Structural & Molecular Biology;Jul2007, Vol. 14 Issue 7, p572 

    MicroRNAs are small, noncoding RNAs that regulate gene expression in eukaryotes. The multipurpose protein hnRNP A1, a well-known factor in the regulation of precursor messenger RNA splicing, has now been implicated in the biogenesis of the microRNA miR-18a, shedding further light on the emerging...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics