The intracellular domain of L1CAM binds to casein kinase 2α and is neuroprotective via inhibition of the tumor suppressors PTEN and p53

Journal of Neurochemistry
Yan Wang, Melitta Schachner

Abstract

Cell adhesion molecule L1 promotes neuritogenesis and neuronal survival through triggering MAPK pathways. Based on the findings that L1 is associated with casein kinase 2 (CK2), and that deficiency in PTEN promotes neuritogenesis in vitro and regeneration after trauma, we examined the functional relationship between L1 and PTEN. In parallel, we investigated the tumor suppressor p53, which also regulates neuritogenesis. Here, we report that the intracellular domain of L1 binds to the subunit CK2α, and that knockdown of L1 leads to CK2 dephosphorylation and an increase in PTEN and p53 levels. Overexpression of L1, but not the L1 mutants L1 (S1181N, E1184V), which reduced binding between L1 and CK2, reduced expression levels of PTEN and p53 proteins, and enhanced levels of phosphorylated CK2α and mammalian target of rapamycin, which is a downstream effector of PTEN and p53. Treatment of neurons with a CK2 inhibitor or transfection with CK2α siRNA increased levels of PTEN and p53, and inhibited neuritogenesis. The combined observations indicate that L1 downregulates expression of PTEN and p53 via direct binding to CK2α. We suggest that L1 stimulates neuritogenesis by activating CK2α leading to decreased levels of PTEN and p53 via a...Continue Reading

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Citations

Sep 25, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jin-Cheng GuoJian-Jun Xie
Jan 13, 2018·International Journal of Oncology·Hayat ZaatitiTamara J Abou-Antoun
Jan 11, 2017·The American Journal of Chinese Medicine·Zhe WeiMelitta Schachner
Aug 28, 2021·Biomolecules·Cian D'Arcy, Christina Kiel
Oct 5, 2021·Autism Research : Official Journal of the International Society for Autism Research·Thomson Patrick JosephMelitta Schachner

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