Regulatory mechanism of cyclins and cyclin-dependent kinases in post-mitotic neuronal cell division

Gupta, Rohan; Jha, A. K.; Ambasta, Rashmi K.; Kumar, Pravir

doi:10.1016/j.lfs.2021.120006

Cited by 12 publications

(6 citation statements)

References 212 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Any disruption in the regulatory program of the cell cycle can result in abnormal cell proliferation [26] . In our study, we investigated whether NUF2 influences classical signaling pathways involved in the cell cycle, such as PI3K/AKT, JAK/STAT3, and JNK/p38 [27] , [28] , [29] . Our study revealed that NUF2 promotes the progression of HCC by regulating the PI3K/AKT signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3

Liu,

Wang,

Wang

et al. 2024

Translational Oncology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3

Liu,

Wang,

Wang

et al. 2024

Translational Oncology

View full text Add to dashboard Cite

“…Instead, Cdk5 activity is mostly present in the nervous system, where it governs virtually all aspects of brain development and neuronal physiology (Allnutt et al, 2020 ; Pao and Tsai, 2021 ). During the last years it has become clear that aberrant cell cycle re-entry in post-mitotic neurons, the ultimate consequence of which is apoptotic cell death, is a common feature in the development of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease (Allnutt et al, 2020 ; Requejo-Aguilar, 2023 ; Gupta et al, 2021 ; Xia et al, 2019 ). Remarkably, Cdk5 plays a central role in this cell cycle reactivation.…”

Section: Discussionmentioning

confidence: 99%

“…Association to p25 causes Cdk5 hyperactivation and mislocalization. This redirects Cdk5 activity to aberrant targets that stimulate cell cycle re-entry in post-mitotic neurons, leading to neuropathological events (Gupta et al, 2021 ; Allnutt et al, 2020 ; Requejo-Aguilar, 2023 ; Joseph et al, 2020 ). Thus, the hyperactivation of Cdk5 is associated with neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

The CDK Pho85 inhibits Whi7 Start repressor to promote cell cycle entry in budding yeast

Ros-Carrero,

Spiridon-Bodi,

Igual

et al. 2024

EMBO Rep

View full text Add to dashboard Cite

Pho85 is a multifunctional CDK that signals to the cell when environmental conditions are favorable. It has been connected to cell cycle control, mainly in Start where it promotes the G1/S transition. Here we describe that the Start repressor Whi7 is a key target of Pho85 in the regulation of cell cycle entry. The phosphorylation of Whi7 by Pho85 inhibits the repressor and explains most of the contribution of the CDK in the activation of Start. Mechanistically, Pho85 downregulates Whi7 protein levels through the control of Whi7 protein stability and WHI7 gene transcription. Whi7 phosphorylation by Pho85 also restrains the intrinsic ability of Whi7 to associate with promoters. Furthermore, although Whi5 is the main Start repressor in normal cycling cells, in the absence of Pho85, Whi7 becomes the major repressor leading to G1 arrest. Overall, our results reveal a novel mechanism by which Pho85 promotes Start through the regulation of the Whi7 repressor at multiple levels, which may confer to Whi7 a functional specialization to connect the response to adverse conditions with the cell cycle control.

show abstract

“…Changes in cell cycle regulators can impede signalling cascades vital for maintaining neuronal transmission and can in some cases lead to neuronal cell death. 26 Evidence has shown that the activation of cyclin-dependent kinases (Cdks), including Cdk2, Cdk4 and Cdk6 in neurons by stress leads to cell cycle re-entry resulting in apoptosis 27 while inhibition of Cdks induces neuroprotective properties. 28 The reduced expression in the prolonged survivors of genes involved in the cell cycle, including the reduction in Cdk expression, specifically Cdk 1 and Cdk8 in the current study may suggest a possible protective mechanism contributing to a reduced pace of motor neuron injury in those patients living longer with ALS.…”

Section: Discussionmentioning

confidence: 99%

Establishing mRNA and microRNA interactions driving disease heterogeneity in amyotrophic lateral sclerosis patient survival

Waller,

Bury,

Appleby-Mallinder

et al. 2023

Brain Communications

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease, associated with the degeneration of both upper and lower motor neurons of the motor cortex, brainstem and spinal cord. Death in most patients results from respiratory failure within 3–4 years from symptom onset. However, due to disease heterogeneity some individuals survive only months from symptom onset while others live for several years. Identifying specific biomarkers that aid in establishing disease prognosis, particularly in terms of predicting disease progression, will help our understanding of amyotrophic lateral sclerosis pathophysiology and could be used to monitor a patient’s response to drugs and therapeutic agents. Transcriptomic profiling technologies are continually evolving, enabling us to identify key gene changes in biological processes associated with disease. MicroRNAs are small non-coding RNAs typically associated with regulating gene expression, by degrading mRNA or reducing levels of gene expression. Being able to associate gene expression changes with corresponding microRNA changes would help to distinguish a more complex biomarker signature enabling us to address key challenges associated with complex diseases such as amyotrophic lateral sclerosis. The present study aimed to investigate the transcriptomic profile (mRNA and microRNA) of lymphoblastoid cell lines from amyotrophic lateral sclerosis patients to identify key signatures that are distinguishable in those patients who suffered a short disease duration (<12 months) (n = 22) compared with those that had a longer disease duration (>6 years) (n = 20). Transcriptional profiling of microRNA–mRNA interactions from lymphoblastoid cell lines in amyotrophic lateral sclerosis patients revealed differential expression of genes involved in cell cycle, DNA damage and RNA processing in patients with longer survival from disease onset compared with those with short survival. Understanding these particular microRNA–mRNA interactions and the pathways in which they are involved may help to distinguish potential therapeutic targets that could exert neuroprotective effects to prolong the life expectancy of amyotrophic lateral sclerosis patients.

show abstract

Regulatory mechanism of cyclins and cyclin-dependent kinases in post-mitotic neuronal cell division

Cited by 12 publications

References 212 publications

NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3

NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3

The CDK Pho85 inhibits Whi7 Start repressor to promote cell cycle entry in budding yeast

Establishing mRNA and microRNA interactions driving disease heterogeneity in amyotrophic lateral sclerosis patient survival

Contact Info

Product

Resources

About