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Most relevant • Gentry, M.s., roMá-Mateo, c., sanz, P. “Laforin, a protein with many faces: glucan
phosphatase, adaptor protein, et alii”. FEBS Journal, 280, 525-537 (2013).
scientific
• rubio-Villena, c., García-GiMeno, M.a. and sanz, P. “Glycogenic activity of R6, a protein
articles
phosphatase 1 regulatory subunit, is modulated by the laforin-malin complex”. Int.
J. Biochem. Cell Biol. 45, 1479-1488 (2013).

• r, t., V, s. s, P. “Sumoylation of AMPKb2 subunit enhances AMP-
ubioerniaand anz
activated protein kinase activity”. Mol. Biol. Cell. 24, 1801-1811 (2013).

• sanchez-Martín, P., raththaGala, M., bridGes, tM., husodo, s., Gentry, M.s., sanz, P. and
r-M, c. “Dimerization of the glucan phosphatase laforin requires the partici-
oMaateo
pation of Cystein 329”. PLoS ONE. 8, e69523 (2013).

• García-GiMenez, J.l., seco-cerVera, M., aGuado, c., roMá-Mateo, c., dasi, F., PrieGo, s.,

MarkoVic, J., knecht, e., sanz, P., Pallardó, F.V. “Lafora disease fibroblasts exemplify
the molecular interdependence between thioredoxin 1 and the proteasome in mam-

malian cells. Free Rad. Biol. Med. 65, 347-359 (2013).

• We have confirmed that residue Cys329 in laforin is essential for the dimerization
Highlights
of the protein. In the absence of this residue either by mutation (C329S) or by

deletion (C329X) a laforin form that is unable to dimerize is obtained. These
results open a door to study the role of the laforin dimerization in cell physiology

[Sanchez-Martin et al., PLoS ONE 8, e69523 (2013)].

• We have identified the protein phosphatase PP1 regulatory subunit R6 (PPP1R3D)

as a new substrate of the laforin-malin complex. This complex ubiquitinates R6

by attaching K63-linked ubiquitin moieties leading to a reduction in its glycogenic
activity [Rubio-Villena et al., Int. J. Biochem. Cell. Biol. 45, 1479-1488 (2013)].

• In laforin deficient cellular models we have detected lower levels of Trx1, what

suggests a possible impairment in the oxidative stress conditions in Lafora

disease patients [Garcia-Gimenez, et al., Free Rad. Biol. Med. 65, 347-359
(2013)].

• We have observed that the AMPKbeta subunit is sumoylated by the E3-SUMO

ligase PIASy. This sumoylation is specific of the AMPKbeta2 isoform, being

absent in AMPKbeta1. This modification increases the kinase activity of the
AMPK trimeric complex and prevents its ubiquitination by E3-ubiquitin ligases

[Rubio et al., Mol Biol Cell. 24, 1801-1811 (2013)].

In addition, I would like to mention the opportunities that were given to present

our work in international forums:
•
First European workshop on AMPK, Maastricht (The Netherlands). Title: The
progressive myoclonus epilepsy of the Lafora type defines novel functions for

AMPK”.
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20
• International Workshop VLC/CAMPUS on intracellular protein degradation in T
OR
neurodegenerative diseases, Valencia (Spain). Title: “Lafora disease, more than P
just a glycogen related disorder”.
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