Three decades of Cdk5

Pao, Ping‐Chieh; Tsai, Li‐Huei

doi:10.1186/s12929-021-00774-y

Cited by 71 publications

(67 citation statements)

References 190 publications

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“…Myristoylatation of the p35/39 helps to associate Cdk5 to vesicles and plasma membrane. Calpain-dependent proteolysis of p35 at the plasma membrane hyperactivates the enzyme (Pao and Tsai, 2021). The enzyme targets a large variety of proteins involved in multiple different pathways (Gao et al, 2021).…”

Section: Phosphoregulation Of Kinesin-3mentioning

confidence: 99%

Phosphoregulation of Kinesins Involved in Long-Range Intracellular Transport

Kumari

Ray

2022

Front. Cell Dev. Biol.

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Kinesins, the microtubule-dependent mechanochemical enzymes, power a variety of intracellular movements. Regulation of Kinesin activity and Kinesin-Cargo interactions determine the direction, timing and flux of various intracellular transports. This review examines how phosphorylation of Kinesin subunits and adaptors influence the traffic driven by Kinesin-1, -2, and -3 family motors. Each family of Kinesins are phosphorylated by a partially overlapping set of serine/threonine kinases, and each event produces a unique outcome. For example, phosphorylation of the motor domain inhibits motility, and that of the stalk and tail domains induces cargo loading and unloading effects according to the residue and context. Also, the association of accessory subunits with cargo and adaptor proteins with the motor, respectively, is disrupted by phosphorylation. In some instances, phosphorylation by the same kinase on different Kinesins elicited opposite outcomes. We discuss how this diverse range of effects could manage the logistics of Kinesin-dependent, long-range intracellular transport.

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Section: Phosphoregulation Of Kinesin-3mentioning

confidence: 99%

Phosphoregulation of Kinesins Involved in Long-Range Intracellular Transport

Kumari

Ray

2022

Front. Cell Dev. Biol.

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“…The kinases displaying the lowest false-discovery rate across the dataset using Fisher’s Exact test were: Atm/Atr, Prkdc (DNA-PKcs), Gsk3-Erk1-2, Cdk5-Cdk and Cdc2b (Fig. 3C); kinases respectively belonging to the DDR, stem cell potency, and cell cycle control (Blackford and Jackson, 2017; Pao and Tsai, 2021; Singh et al, 2012). We note that Gsk3-Erk1-2 phosphorylation differences were expected given the maintenance of primed and naïve stem cell states requires culture modulation of FGF, activin, and LIF, which signal through Gsk3-Erk1-2 pathways (Cho et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Replication stress tolerance and management differs between naïve and primed pluripotent cells

Kafer

O’Connor

Rogers

et al. 2022

Preprint

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SummaryReplication stress is an endemic threat to genome stability. For reasons unknown, replication stress response factors become essential during peri-implantation development. This coincides with a stem cell potency switch from the naïve to the primed state. Using genetically matched, chimera-derived mouse naïve embryonic (mESC) and primed epiblast stem cells (mEpiSC) we found that replication stress management differs between potency states. Primed mEpiSCs rely on Atr activity to prevent replication catastrophe, minimize genomic damage, avoid apoptosis, and re-enter the cell cycle. Conversely, under replications stress, mESCs readily activate Atm regardless of Atr activity, undergo replication catastrophe, and induce apoptosis. Primed pluripotent cells therefore engage Atr to counteract replication difficulties and maintain viability, whereas cells in the naïve state are more readily cleared under the same conditions. We anticipate these divergent strategies enable pluripotent cells of different potency states to meet associated proliferative or developmental demands during early development.

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“…Studies have revealed that neuroprotection is correlated with the inhibition of neuron-specific CDK5 [64]. For neurite outgrowth and cortical lamination, CDK5 and its neuron-specific activator p35 are essential [65]. Proteolytic cleavage of CDK 5 activator p35 by calpain led to the formation and accumulation of p25 in the brain of AD patients [66].…”

Section: Phyto-carbazole Alkaloids From the Genus Clausenamentioning

confidence: 99%

Phyto-Carbazole Alkaloids from the Rutaceae Family as Potential Protective Agents against Neurodegenerative Diseases

Tan

Sharma

2022

Antioxidants

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Plant-derived (phyto) carbazole alkaloids are an important class of compounds, presented in the family of Rutaceae (Genera Murraya, Clausena, Glycosmis, Micromelum and Zanthoxylum). Due to several significant biological activities, such as antitumor, antibacterial, antiviral, antidiabetic, anti-HIV and neuroprotective activities of the parent skeleton (3-methylcarbazole), carbazole alkaloids are recognized as an important class of potential therapeutic agents. Neurodegenerative diseases (NDs) may exhibit a vast range of conditions, affecting neurons primarily and leading ultimately to the progressive losses of normal motor and cognitive functions. The main pathophysiological indicators of NDs comprise increasing atypical protein folding, oxidative stresses, mitochondrial dysfunctions, deranged neurotransmissions and neuronal losses. Phyto-carbazole alkaloids can be investigated for exerting multitarget approaches to ameliorating NDs. This review presents a comprehensive evaluation of the available scientific literature on the neuroprotective mechanisms of phyto-carbazole alkaloids from the Rutaceae family in ameliorating NDs.

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Three decades of Cdk5

Cited by 71 publications

References 190 publications

Phosphoregulation of Kinesins Involved in Long-Range Intracellular Transport

Phosphoregulation of Kinesins Involved in Long-Range Intracellular Transport

Replication stress tolerance and management differs between naïve and primed pluripotent cells

Phyto-Carbazole Alkaloids from the Rutaceae Family as Potential Protective Agents against Neurodegenerative Diseases

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