Journal article

Phosphorylation of hnRNP K by cyclin-dependent kinase 2 controls cytosolic accumulation of TDP-43

Diane Moujalled, Janine L James, Shu Yang, Katharine Zhang, Clare Duncan, Donia M Moujalled, Sarah J Parker, Aphrodite Caragounis, Grace Lidgerwood, Bradley J Turner, Julie D Atkin, Alexandra Grubman, Jeffrey R Liddell, Christian Proepper, Tobias M Boeckers, Katja M Kanninen, Ian Blair, Peter J Crouch, Anthony R White

HUMAN MOLECULAR GENETICS | OXFORD UNIV PRESS | Published : 2015

Abstract

Cytosolic accumulation of TAR DNA binding protein 43 (TDP-43) is a major neuropathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms involved in TDP-43 accumulation remain largely unknown. Previously, we reported that inhibitors of cyclin-dependent kinases (CDKs) prevented cytosolic stress granule accumulation of TDP-43, correlating with depletion of heterogeneous ribonucleoprotein (hnRNP) K from stress granules. In the present study, we further investigated the relationship between TDP-43 and hnRNP K and their control by CDKs. Inhibition of CDK2 abrogated the accumulation of TDP-43 into stress granules. Phosphorylate..

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Grants

Awarded by Helmholtz Society (DZNE)


Awarded by Australian Research Council Future Fellowship


Funding Acknowledgements

This work was supported by the Motor Neuron Disease Research Institute of Australia (Terry Quinn and Cliff Smith MND Research Grants) (to A.R.W.), Australian Rotary Health (to J.J.), and Orion-Farmos Research Foundation (to K.M.K.), the Helmholtz Society (DZNE, VH-VI-510, 'RNA dysmetabolism in ALS and FTD') and the BMBF (MND-NET) to TMB. A.R.W. is a recipient of an Australian Research Council Future Fellowship (DP110101368). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.