scholarly journals Post-translational modifications of CDK5 and their biological roles in cancer

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Gui-Bin Gao ◽  
Yue Sun ◽  
Run-Dong Fang ◽  
Ying Wang ◽  
Yang Wang ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Malignant Tumors ◽  
Biological Significance ◽  
Cyclin Dependent Kinase ◽  
Antitumor Effects ◽  
Aberrant Expression ◽  
Post Translational Modifications ◽  
Atypical Member ◽  
Cyclin Dependent Kinase 5

AbstractPost-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its aberrant expression links to cell proliferation, DNA damage response, apoptosis, migration and angiogenesis in cancer. Current studies suggested that, new PTMs on CDK5, including S-nitrosylation, sumoylation, and acetylation, serve as molecular switches to control the kinase activity of CDK5 in the cell. However, a majority of these modifications and their biological significance in cancer remain uncharacterized. In this review, we discussed the role of PTMs on CDK5-mediated signaling cascade, and their possible mechanisms of action in malignant tumors, as well as the challenges and future perspectives in this field. On the basis of the newly identified regulatory signaling pathways of CDK5 related to PTMs, researchers have investigated the cancer therapeutic potential of chemical compounds, small-molecule inhibitors, and competitive peptides by targeting CDK5 and its PTMs. Results of these preclinical studies demonstrated that targeting PTMs of CDK5 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted.

scholarly journals A kinase of many talents: non-neuronal functions of CDK5 in development and disease

Open Biology ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 190287 ◽  
Author(s):  
Samanta Sharma ◽  
Piotr Sicinski
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinases ◽  
The Family ◽  
Neuronal Tissues ◽  
Neuronal Functions ◽  
Cyclin Dependent Kinase 5

The cyclin-dependent kinase 5 (CDK5) represents an unusual member of the family of cyclin-dependent kinases, which is activated upon binding to non-cyclin p35 and p39 proteins. The role of CDK5 in the nervous system has been very well established. In addition, there is growing evidence that CDK5 is also active in non-neuronal tissues, where it has been postulated to affect a variety of functions such as the immune response, angiogenesis, myogenesis, melanogenesis and regulation of insulin levels. Moreover, high levels of CDK5 have been observed in different tumour types, and CDK5 was proposed to play various roles in the tumorigenic process. In this review, we discuss these various CDK5 functions in normal physiology and disease, and highlight the therapeutic potential of targeting CDK5.

scholarly journals The Role of TGF-β Signaling Pathways in Cancer and Its Potential as a Therapeutic Target

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yun Yang ◽  
Wen-Long Ye ◽  
Ruo-Nan Zhang ◽  
Xiao-Shun He ◽  
Jing-Ru Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Immune Escape ◽  
Therapeutic Potential ◽  
Malignant Tumors ◽  
Transforming Growth Factor Β ◽  
Antitumor Effects ◽  
Downstream Signaling

The transforming growth factor-β (TGF-β) signaling pathway mediates various biological functions, and its dysregulation is closely related to the occurrence of malignant tumors. However, the role of TGF-β signaling in tumorigenesis and development is complex and contradictory. On the one hand, TGF-β signaling can exert antitumor effects by inhibiting proliferation or inducing apoptosis of cancer cells. On the other hand, TGF-β signaling may mediate oncogene effects by promoting metastasis, angiogenesis, and immune escape. This review summarizes the recent findings on molecular mechanisms of TGF-β signaling. Specifically, this review evaluates TGF-β′s therapeutic potential as a target by the following perspectives: ligands, receptors, and downstream signaling. We hope this review can trigger new ideas to improve the current clinical strategies to treat tumors related to the TGF-β signaling pathway.

RegulatING chromatin regulators: post-translational modification of the ING family of epigenetic regulators

2013 ◽  
Vol 450 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Shankha Satpathy ◽  
Arash Nabbi ◽  
Karl Riabowol
Keyword(s):  
Biological Significance ◽  
Type Ii ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Chromatin Regulators ◽  
Cancer Types ◽  
Splicing Isoforms ◽  
Enrichment Techniques ◽  
Affect Cell Growth

The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine-tuned in the physiological setting and how they add to the repertoire of activities affected by the INGs. In the present paper we review the different PTMs that have been reported to occur on INGs. We discuss the PTMs that modulate ING function under normal conditions and in response to a variety of stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes including subcellular localization, interaction with enzymatic complexes and ING protein half-life. The present review aims to highlight the emerging role of PTMs in regulating ING function and to suggest additional pathways and functions where PTMs may effect ING function.

Role of cyclin-dependent kinase 5 in capsaicin-induced cough

2007 ◽  
Vol 566 (1-3) ◽  
pp. 181-184 ◽  
Author(s):  
Junzo Kamei ◽  
Shun-suke Hayashi ◽  
Yoshiki Takahashi ◽  
Chihiro Nozaki
Keyword(s):  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5

Alzheimer Disease and Related Tauopathies: Possible Neuroprotective Strategies

2018 ◽  
Vol 2 (3) ◽  
pp. 01-02
Author(s):  
Meketa Muñoz
Keyword(s):  
Alzheimer Disease ◽  
Glycogen Synthase ◽  
Vital Role ◽  
Current Therapy ◽  
Cyclin Dependent Kinase ◽  
Abnormal Hyperphosphorylation ◽  
Neuroprotective Strategies ◽  
Gsk 3Β ◽  
Cyclin Dependent Kinase 5

Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.

scholarly journals IGFBP-3/IGFBP-3 Receptor System as an Anti-Tumor and Anti-Metastatic Signaling in Cancer

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1261 ◽  
Author(s):  
Qing Cai ◽  
Mikhail Dozmorov ◽  
Youngman Oh
Keyword(s):  
Therapeutic Potential ◽  
Transmembrane Protein ◽  
Biological Significance ◽  
Cell Types ◽  
Receptor System ◽  
Post Translational Modifications ◽  
Major Carrier ◽  
Assay Methods ◽  
Underlying Mechanisms ◽  
Igfbp 3

Insulin-like growth factor binding protein-3 (IGFBP-3) is a p53 tumor suppressor-regulated protein and a major carrier for IGFs in circulation. Among six high-affinity IGFBPs, which are IGFBP-1 through 6, IGFBP-3 is the most extensively investigated IGFBP species with respect to its IGF/IGF-I receptor (IGF-IR)-independent biological actions beyond its endocrine/paracrine/autocrine role in modulating IGF action in cancer. Disruption of IGFBP-3 at transcriptional and post-translational levels has been implicated in the pathophysiology of many different types of cancer including breast, prostate, and lung cancer. Over the past two decades, a wealth of evidence has revealed both tumor suppressing and tumor promoting effects of IGF/IGF-IR-independent actions of IGFBP-3 depending upon cell types, post-translational modifications, and assay methods. However, IGFBP-3′s anti-tumor function has been well accepted due to identification of functional IGFBP-3-interacting proteins, putative receptors, or crosstalk with other signaling cascades. This review mainly focuses on transmembrane protein 219 (TMEM219), which represents a novel IGFBP-3 receptor mediating antitumor effect of IGFBP-3. Furthermore, this review delineates the potential underlying mechanisms involved and the subsequent biological significance, emphasizing the clinical significance of the IGFBP-3/TMEM219 axis in assessing both the diagnosis and the prognosis of cancer as well as the therapeutic potential of TMEM219 agonists for cancer treatment.

Is there a role of the cyclin-dependent kinase 5 activator p25 in Alzheimer??s disease?

Neuroreport ◽  
2005 ◽  
Vol 16 (16) ◽  
pp. 1725-1730 ◽  
Author(s):  
K. Peter Giese ◽  
Laurence Ris ◽  
Florian Plattner
Keyword(s):  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5

scholarly journals Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo-Qiang Wang ◽  
Cheng Cen ◽  
Chong Li ◽  
Shuai Cao ◽  
Ning Wang ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Prelimbic Cortex ◽  
Cyclin Dependent Kinase ◽  
Pain Sensation ◽  
Pain Model ◽  
Excitatory Neurons ◽  
Affective Pain ◽  
Underlying Mechanisms ◽  
Cyclin Dependent Kinase 5

Abstract The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.

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