2024-03-29T07:29:08Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/390192022-06-30T11:47:05Zcom_10261_109com_10261_1col_10261_362
Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level
Romá-Mateo, Carlos
Moreno, Daniel
Vernia, Santiago
Rubio, Teresa
Bridges, Travis M.
Gentry, Matthew S.
Sanz, Pascual
Abstract Background Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin. Results After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming a functional complex, laforin and perhaps malin may also have independent functions. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32, which belongs to the tripartite-motif containing family of proteins. We present experimental evidence that both malin and TRIM32 share some substrates for ubiquitination, although they produce ubiquitin chains with different topologies. However, TRIM32-specific substrates were not reciprocally ubiquitinated by the laforin-malin complex. Conclusions We found that malin and laforin are not conserved in the same genomes. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32. The latter result suggests a common origin for malin and TRIM32 and provides insights into possible functional relationships between both proteins.
This work was supported by a grant from the Spanish Ministry of Education and Science (SAF2008-01907) to PS; and by National Institutes of Health grants 5R00NS061803, 5P20RR0202171, 1R01NS070899 and University of Kentucky College of Medicine startup funds to M.S.G.
Peer Reviewed
2011-08-26T13:26:51Z
2011-08-26T13:26:51Z
2011-07-28
2011-08-26T13:26:51Z
artículo
http://purl.org/coar/resource_type/c_6501
http://dx.doi.org/10.1186/1471-2148-11-225
BMC Evolutionary Biology. 11(1):225 (2011)
http://hdl.handle.net/10261/39019
en
Publisher’s version
open
BioMed Central