Kozakova, Lucie, Vondrova, Lucie, Stejskal, Karel, Charalabous, Panagoula, Kolesar, Peter, Lehmann, Alan R, Uldrijan, Stjepan, Sanderson, Christopher M, Zdrahal, Zbynek and Palecek, Jan J (2015) The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex. Cell Cycle, 14 (6). pp. 920-930. ISSN 1538-4101

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Abstract

The MAGE (Melanoma-associated antigen) protein family members are structurally related to each other by a MAGEhomology domain comprised of 2 winged helix motifs WH/A and WH/B. This family specifically evolved in placental mammals although single homologs designated NSE3 (non-SMC element) exist in most eukaryotes. NSE3, together with its partner proteins NSE1 and NSE4 form a tight subcomplex of the structural maintenance of chromosomes SMC5–6 complex. Previously, we showed that interactions of the WH/B motif of the MAGE proteins with their NSE4/EID partners are evolutionarily conserved (including the MAGEA1-NSE4 interaction). In contrast, the interaction of the WH/A motif of NSE3 with NSE1 diverged in the MAGE paralogs. We hypothesized that the MAGE paralogs acquired new RING-finger containing partners through their evolution and form MAGE complexes reminiscent of NSE1-NSE3-NSE4 trimers. In this work, we employed the yeast 2-hybrid system to screen a human RING-finger protein library against several MAGE baits. We identified a number of potential MAGE-RING interactions and confirmed several of them (MDM4, PCGF6, RNF166, TRAF6, TRIM8, TRIM31, TRIM41) in co-immunoprecipitation experiments. Among these MAGE-RING pairs, we chose to examine MAGEA1-TRIM31 in detail and showed that both WH/A and WH/B motifs of MAGEA1 bind to the coiled-coil domain of TRIM31 and that MAGEA1 interaction stimulates TRIM31 ubiquitin-ligase activity. In addition, TRIM31 directly binds to NSE4, suggesting the existence of a TRIM31-MAGEA1-NSE4 complex reminiscent of the NSE1-NSE3-NSE4 trimer. These results suggest that MAGEA1 functions as a co-factor of TRIM31 ubiquitin-ligase and that the TRIM31-MAGEA1-NSE4 complex may have evolved from an ancestral NSE1-NSE3-NSE4 complex.

Item Type:	Article
Keywords:	E3 ubiquitin ligase, MAGEA1, Melanoma-associated antigen family, MDM4, NSE1-NSE3-NSE4 complex, NSE4/EID family, Protein evolution, PCGF6, RING-finger proteins, RNF166, TRIM31, TRIM family, TRAF6, TRIM8, TRIM41, Ubiquitination
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects:	Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User:	Gee Wheatley
Date Deposited:	31 Jul 2015 14:51
Last Modified:	05 Aug 2019 11:35
URI:	http://sro.sussex.ac.uk/id/eprint/55911

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