RASHMI PARIHAR
Articles written in Journal of Biosciences
Volume 40 Issue 5 December 2015 pp 863-871 Articles
Shuchi Mittal Mamta Upadhyay Pankaj Kumar Singh Rashmi Parihar Subramaniam Ganesh
Lafora disease (LD), an autosomal recessive and fatal form of neurodegenerative disorder, is characterized by the presence of polyglucosan inclusions in the affected tissues including the brain. LD can be caused by defects either in the 𝐸𝑃𝑀2𝐴 gene coding for the laforin protein phosphatase or the 𝑁𝐻𝐿𝑅𝐶𝐼 gene coding for the malin ubiquitin ligase. Since the clinical symptoms of LD patients representing the two genetic groups are very similar and since malin is known to interact with laforin, we were curious to examine the possibility that the two proteins regulate each others function. Using cell biological assays we demonstrate here that
malin promotes its own degradation via auto-ubiquitination,
laforin prevents the auto-degradation of malin by presenting itself as a substrate and
malin preferentially degrades the phosphatase-inactive laforin monomer. Our results that laforin and malin regulate each others stability and activity offers a novel and attractive model to explain the molecular basis of locus heterogeneityobserved in LD.
Volume 43 Issue 4 September 2018 pp 817-818 Correction
SHUCHI MITTAL MAMTA UPADHYAY PANKAJ KUMAR SINGH RASHMI PARIHAR SUBRAMANIAM GANESH
Volume 48, 2023
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