2024-03-28T14:52:22Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1259202021-12-27T16:29:30Zcom_10261_109com_10261_1col_10261_362
The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2
Viana, Rosa
Luján, Pablo
Sanz, Pascual
Ministerio de Educación, Cultura y Deporte (España)
Generalitat Valenciana
[Background] Lafora disease (LD, OMIM 254780) is a fatal neurodegenerative disorder produced mainly by mutations in two genes: EPM2A, encoding the dual specificity phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. Although it is known that laforin and malin may form a functional complex, the underlying molecular mechanisms of this pathology are still far from being understood.
[Methods] In order to gain information about the substrates of the laforin/malin complex, we have carried out a yeast substrate-trapping screening, originally designed to identify substrates of protein tyrosine phosphatases.
[Results] Our results identify the two muscular isoforms of pyruvate kinase (PKM1 and PKM2) as novel interaction partners of laforin.
[Conclusions] We present evidence indicating that the laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2. This post-translational modification, although it does not affect the catalytic activity of PKM1, it impairs the nuclear localization of PKM2.
2015-11-25T17:57:19Z
2015-11-25T17:57:19Z
2015-10-23
2015-11-25T17:57:19Z
artículo
BMC Biochemistry 16(1): 24 (2015)
1471-2091
http://hdl.handle.net/10261/125920
10.1186/s12858-015-0053-6
http://dx.doi.org/10.13039/501100003176
http://dx.doi.org/10.13039/501100003359
26493215
en
Publisher's version
http://dx.doi.org/10.1186/s12858-015-0053-6
Sí
Viana et al.
http://creativecommons.org/licenses/by/4.0/
openAccess
BioMed Central