FKBPL and FKBP8 regulate DLK degradation and neuronal responses to axon injury
Lee, B.; Oh, Y.; Cho, E.; DiAntonio, A.; Cavalli, V.; Shin, J. E.; Cho, Y.
Show abstract
DLK is a key regulator of axon regeneration and degeneration in response to neuronal injury. To understand the molecular mechanisms controlling the DLK function, we performed yeast two-hybrid screening analysis and identified FKBPL as a DLK-binding protein that bound to the kinase domain and inhibited the kinase enzymatic activity of DLK. FKBPL regulated DLK stability through ubiquitin-dependent DLK degradation. We tested other members in the FKBP protein family and found that FKBP8 also induced DLK degradation as FKBPL did. We found that Lysine 271 residue in the kinase domain of DLK was a major site of ubiquitination and SUMO3-conjugation and responsible for FKBP8-mediated degradation. In vivo overexpression of FKBP8 delayed progression of axon degeneration and neuronal death following axotomy in sciatic and optic nerves, respectively, although axon regeneration efficiency was not enhanced. This research identified FKBPL and FKBP8 as new DLK-interacting proteins that regulated DLK stability by MG-132 or bafilomycin A1-sensitive protein degradation.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- DBT is a metabolic switch for maintenance of proteostasis under proteasomal impairment 96%
- FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1 95%
- Styxl2 regulates de novo sarcomere assembly by binding to non-muscle myosin IIs and promoting their degradation 94%
Similar papers in this journal
- Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration 94%
- Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2 93%
- Increased burden of rare risk variants across gene expression networks predisposes to sporadic Parkinson's disease 93%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.