Cyclin Dependent Kinase 5 Cdk5

Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.

Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.

A high-affinity inhibitor protein called CIP, which can be produced by small truncations of p35, was earlier identified by Amin, Albers, and Pant. P35 is one of the physiological activators of cdk5, a member of the cyclin-dependent kinase family. These proteins are known to be associated with the hyperphosphorylation of specific neuronal proteins. This typically occurs in the case of neurodegenerative diseases such as Alzheimer s. In this paper the authors study in silico the binding mechanism of cdk5-p25 and cdk5-CIP complexes more in detail. This provides a better understanding of the inhibitory activity of the protein CIP. The authors use a geometry-based technique to verify the following hypothesis: p25 s truncation provides increased flexibility to CIP, and hence CIP is able to conform better to cdk5 interface than p25 is. Therefore CIP is expected to bind to cdk5 more easily than p25 and prevent it from reaching its active conformation. The authors' in silico study is based on a geometry-based alignment algorithm. The algorithm is capable of efficiently aligning two protein conformations with respect to their interfaces, which are represented as point sets. The algorithm is based on biochemical criteria as well as geometrical ones.

Cdk5 is a unique member of a family of serine/threonine cyclin-dependent kinases. Although Cdk5 is ubiquitously expressed, this kinase is predominantly active in post-mitotic neurons where there is abundant expression of its obligate activating partners p35 and/or p39. Consequently, Cdk5 has been historically considered a 'neuron-specific' kinase and recognized as an essential regulator of neuronal functions. However, aberrant Cdk5 activity has be associated with a variety of inflammatory neurodegenerative disorders and activity of the Cdk5-p35 complex has been associated with disorders involving non-neuronal tissues, indicating the potential for novel extra-neuronal roles for Cdk5. Our work describes a previously unknown function of the Cdk5-p35 complex in T cells. We demonstrate the activity of Cdk5 is required for the induction of EAE, a T-cell-mediated neuro-inflammatory disease model of multiple sclerosis. Activation of T cells leads to an induction of Cdk5-p35 expression that we show is essential for optimal T cell function. In an effort to define mechanisms mediating this effect of Cdk5, we discovered that Cdk5 controls IL2 gene expression during T-cell activation by modulating the HDAC1/mSin3a repressor complex. We show this effect of Cdk5 is dependent on specific phosphorylation of the mSin3a protein at serine 861. Disruption of Cdk5 activity in T cells results in enhanced HDAC activity and binding of the HDAC1/mSin3a repressor complex to the IL2 promoter and subsequently leads to the suppression of IL2 expression. In our pursuit of alternative mechanisms, we focused on Foxp3+ regulatory T cells (Tregs) whose activity is essential for maintaining immune homeostasis and controlling inflammation in the CNS. We show that Cdk5 activity is a determinant of the expression of Foxp3 in CD4+ T cells, effectively regulating the differentiation of Tregs in the presence of pro-inflammatory factors. Our data show the IL-6 induced repression of Foxp3 gene expression requires Cdk5-mediated phosphorylation of Stat3 specifically at residue 727. Taken together, the studies described here define novel and important functions of Cdk5-p35 in T cells, and suggest the potential to exploit this biology through the preclinicalclinical development of Cdk5 as a target for therapeutic intervention against T-cell mediated autoimmune and chronic inflammatory diseases.

Cyclin-Dependent Kinases—Advances in Research and Application: 2013 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about ZZZAdditional Research in a compact format. The editors have built Cyclin-Dependent Kinases—Advances in Research and Application: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about ZZZAdditional Research in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Cyclin-Dependent Kinases—Advances in Research and Application: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.

CDC2-CDC28 Kinases—Advances in Research and Application: 2012 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about CDC2-CDC28 Kinases in a compact format. The editors have built CDC2-CDC28 Kinases—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about CDC2-CDC28 Kinases in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of CDC2-CDC28 Kinases—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.