Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cycline‐dependent kinase 5 complexes

@article{Asada2008MyristoylationOP,
  title={Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cycline‐dependent kinase 5 complexes},
  author={Akiko Asada and Naoyuki Yamamoto and Masaki Gohda and Taro Saito and Nobuhiro Hayashi and Shin-ichi Hisanaga},
  journal={Journal of Neurochemistry},
  year={2008},
  volume={106}
}
Cdk5 is a member of the cyclin‐dependent kinases (Cdks), activated by the neuron‐specific activator p39 or p35. The activators also determine the cytoplasmic distribution of active Cdk5, but the mechanism is not yet known. In particular, little is known for p39. p39 and p35 contain localization motifs, such as a second Gly for myristoylation and Lys clusters in the N‐terminal p10 region. Using mutant constructs, we investigated the cellular distribution mechanism. We observed that p39 localizes… 
Phosphorylation of p35 and p39 by Cdk5 determines the subcellular location of the holokinase in a phosphorylation-site-specific manner
TLDR
The results suggest that the subcellular localization of the Cdk5-activator complexes is determined by its kinase activity, and also implicate a role for p39–Cdk5 in the nucleus.
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TLDR
The results suggest that p39-Cdk5 has a dominant role in Rac1-dependent lamellipodial activity and it is determined that the localization of p39 to lameLLipodia requires myristoylation and Lys clusters within the N-terminal p10 region.
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TLDR
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TLDR
The structural basis for the instability of p39-Cdk5 is caused by decreased hydrogen bond interaction, and the difference in the hydrogen bond network contributes to the different properties between Cdk5 and its activators.
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TLDR
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p35 Regulates the CRM1-Dependent Nucleocytoplasmic Shuttling of Nuclear Hormone Receptor Coregulator-Interacting Factor 1 (NIF-1)
TLDR
The results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway, and identify a nuclear export signal on p35, revealing a new p35-dependent mechanism in transcriptional regulation that involves the nucleocy toplasmics shuttling of transcription regulators.
Ubiquitin-independent degradation of p 35 1 Two degradation pathways of the p 35 Cdk 5 activation subunit , dependent and independent of ubiquitination
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p10, the N-terminal domain of p35, protects against CDK5/p25-induced neurotoxicity
TLDR
It is shown that a peptide (p10′) encoding the N-terminal domain of p35 protects against CDK5/p25-induced toxicity in neurons, and suggests that p10 (protein of 10 kDa) is a unique prosurvival domain in p35, essential for normal CDK 5/p35 function in neurons.
Sumoylation of p35 Modulates p35/Cyclin-Dependent Kinase (Cdk) 5 Complex Activity
TLDR
It is shown that sumoylation is a likely candidate mechanism for the rapid modulation of p35/Cdk5 activity in physiological situations as well as in disease.
Erratum: Cyclin I-like (CCNI2) is a cyclin-dependent kinase 5 (CDK5) activator and is involved in cell cycle regulation
TLDR
This Article contains errors in the Reference list, and the references following the sentence "Several groups showed independently that CDK5 could regulate cell cycle 26,27,34–37 " should read: " Several groups showed independent that CDk5 could regulating cell cycle 25,34-37".
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References

SHOWING 1-10 OF 50 REFERENCES
Cdk5–p39 is a labile complex with the similar substrate specificity to Cdk5–p35
TLDR
A method for purifying kinase‐active Cdk5–p39 from Sf9 cells infected with baculovirus encoding Cdk 5 and p39 showed similar substrate specificity to that of Cdk3–p35, but with opposite sensitivity to detergent, suggesting their distinct roles under different regulation mechanisms in neurons.
p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton.
TLDR
It is shown here that p39 associates with cdk5 in brain lysates, and that this complex is active in phosphorylation of histone H1, and suggested that it might play a role in regulating actin cytoskeletal dynamics in cells.
Suppression of Calpain-dependent Cleavage of the CDK5 Activator p35 to p25 by Site-specific Phosphorylation*
TLDR
Results suggest phosphorylation of Thr138 predominantly defines the susceptibility of p35 to calpain-dependent cleavage and that dephosphorylated of this site is a critical determinant of Cdk5-p25-induced cell death associated with neurodegeneration.
Identification of Nuclear Import Mechanisms for the Neuronal Cdk5 Activator*
TLDR
The results suggest that p35 employs pathways distinct from that used by Cdk5 for transport to the nucleus, and shows that the nuclear localization of p35 does not require the association of Cdk 5.
The Regulation of Cyclin-Dependent Kinase 5 Activity through the Metabolism of p35 or p39 Cdk5 Activator
TLDR
Phosphorylation of p35 modulates its proteolytic pattern, stimulates proteasomal degradation and suppresses calpain cleavage, and how the metabolism of p39 is regulated, however, is a future problem to be investigated.
The Cdk5‐p35 kinase associates with the Golgi apparatus and regulates membrane traffic
TLDR
A novel subcellular localization of this kinase is shown and a role for Cdk5‐p35 in membrane traffic during neuronal process outgrowth is suggested and it is suggested that the formation of membrane vesicles from the Golgi apparatus is blocked.
Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration
TLDR
It is found that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease, and this accumulation correlates with an increase in Cdk5 kinase activity.
Activation of latent cyclin‐dependent kinase 5 (Cdk5)–p35 complexes by membrane dissociation
TLDR
This work has examined membrane interactions as one method of regulating the Cdk5–p35 complex, a Ser/Thr kinase of increasingly recognized importance in a large number of fields, ranging from neuronal migration to synaptic plasticity and neurodegeneration.
Cdk5 phosphorylates p53 and regulates its activity
TLDR
It is shown that in apoptotic PC12 cells the levels of p53 and Cdk5 increase concomitantly, and it is the first demonstration that p53 is a substrate of Cdk4, and that Cdk 5 can modulate p53 levels and activity.
Precursor of cdk5 activator, the 23 kDa subunit of tau protein kinase II: Its sequence and developmental change in brain
TLDR
Findings suggest that p23 results from the processing of the precursor protein, pre‐p23, suggesting that its expression controls the phosphorylation of tau by the TPKII/TPKI system in the neonatal brain.
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