Extraneuronal activities and regulatory mechanisms of the atypical cyclin-dependent kinase Cdk5

Arif, Abul

doi:10.1016/j.bcp.2012.06.027

Cited by 79 publications

(69 citation statements)

References 85 publications

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“…Emerging evidence indicates that CDK5 may have extraneuronal functions that comprise transcript-selective translation control, glucose-inducible insulin secretion, vascular angiogenesis, cell adhesion, migration, and wound healing (12,(17)(18)(19). Importantly, CDK5 also plays critical roles in the development and progression of many types of human cancers, which include liver cancer (20), colorectal cancer (21), pancreatic cancer (16,22), prostate cancer (23,24), and lung cancer (25,26).…”

mentioning

confidence: 99%

Proteomic Analysis of the Human Cyclin-dependent Kinase Family Reveals a Novel CDK5 Complex Involved in Cell Growth and Migration

Wang

et al. 2014

Molecular & Cellular Proteomics

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Cyclin-dependent kinases (CDKs) are the catalytic subunits of a family of mammalian heterodimeric serine/threonine kinases that play critical roles in the control of cell-cycle progression, transcription, and neuronal functions. However, the functions, substrates, and regulation of many CDKs are poorly understood. To systematically investigate these features of CDKs, we conducted a proteomic analysis of the CDK family and identified their associated protein complexes in two different cell lines using a modified SAINT (Significance Analysis of INTeractome) method. The mass spectrometry data were deposited to ProteomeXchange with identifier PXD000593 and DOI 10.6019/PXD000593. We identified 753 high-confidence candidate interaction proteins (HCIPs) in HEK293T cells and 352 HCIPs in MCF10A cells. We subsequently focused on a neuron-specific CDK, CDK5, and uncovered two novel CDK5-binding partners, KIAA0528 and fibroblast growth factor (acidic) intracellular binding protein (FIBP), in non-neuronal cells. We showed that these three proteins form a stable complex, with KIAA0528 and FIBP being required for the assembly and stability of the complex. Furthermore, CDK5-, KIAA0528-, or FIBP-depleted breast cancer cells displayed impaired proliferation and decreased migration, suggesting that this complex is required for cell growth and migration in non-neural cells. Our study uncovers new aspects of CDK functions, which provide direction for further investigation of these critical protein kinases. Molecular & Cellular

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confidence: 99%

Proteomic Analysis of the Human Cyclin-dependent Kinase Family Reveals a Novel CDK5 Complex Involved in Cell Growth and Migration

Wang

et al. 2014

Molecular & Cellular Proteomics

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“…CDK5 plays a critical role in regulating a number of vital cellular processes including cell, survival and migration in a variety of cell types, including lymphoid cells (1,(5)(6)(7). Deregulation of CDK5 activity is associated with the pathology of cancer, inflammation, diabetes and protein folding diseases including Alzheimer disease, amyotrophic lateral sclerosis, and Parkinson disease.…”

Section: Discussionmentioning

confidence: 99%

“…CDK5 was originally believed to be restricted to neuronal cells where it plays fundamental roles in brain development through regulation of cell migration, neurite outgrowth, and synapse formation (1,2). However, CDK5 also regulates numerous activities in a wide variety of non-neuronal cells including lymphocytes (5)(6)(7).…”

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confidence: 99%

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Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression

Morey

Roufayel

Johnston

et al. 2015

Journal of Biological Chemistry

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Background: HSP70 inhibits heat-induced apoptosis by preventing NOXA accumulation. Results: Inhibition of CDK5 in heat-shocked cells reduces levels of miR-23a leading to increased NOXA abundance, which is prevented by HSP70. Conclusion: CDK5 regulates miR-23a expression and affects NOXA abundance. Significance: The prosurvival function of HSP70 can be attributed to its ability to prevent the stress-induced inhibition of CDK5.

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“…p35 and p39 expression are observed in multiple non-neuronal cells, such as T cells, macrophages, muscle cells, neutrophils, and pancreatic cells (Contreras-Vallejos et al, 2012). They regulate gene expression, glucose-inducible secretion, hematopoietic cell differentiation, vascular angiogenesis, cell migration, and immune responses (Arif, 2012). p35 and p39 may also be expressed in astrocytes and microglia Fang et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination

Luo¹,

Zhang²,

Burke

et al. 2016

J. Neurosci.

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The regulation of oligodendrocyte development and myelin formation in the CNS is poorly defined. Multiple signals influence the rate and extent of CNS myelination, including the noncanonical cyclin-dependent kinase 5 (Cdk5) whose functions are regulated by its activators p35 and p39. Here we show that selective loss of either p35 or p39 perturbed specific aspects of oligodendrocyte development, whereas loss of both p35 and p39 completely inhibited the development of mature oligodendrocytes and myelination. In the absence of p35, oligodendrocyte differentiation was delayed, process outgrowth was truncated in vitro, and the patterning and extent of myelination were perturbed in the CNS of p35 Ϫ/Ϫ mice. In the absence of p39, oligodendrocyte maturation was transiently affected both in vitro and in vivo. However, loss of both p35 and p39 in oligodendrocyte lineage cells completely inhibited oligodendrocyte progenitor cell differentiation and myelination both in vitro and after transplantation into shiverer slice cultures. Loss of p35 and p39 had a more profound effect on oligodendrocyte development than simply the loss of Cdk5 and could not be rescued by Cdk5 overexpression. These data suggest p35 and p39 have specific and overlapping roles in oligodendrocyte development, some of which may be independent of Cdk5 activation.

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Extraneuronal activities and regulatory mechanisms of the atypical cyclin-dependent kinase Cdk5

Cited by 79 publications

References 85 publications

Proteomic Analysis of the Human Cyclin-dependent Kinase Family Reveals a Novel CDK5 Complex Involved in Cell Growth and Migration

Proteomic Analysis of the Human Cyclin-dependent Kinase Family Reveals a Novel CDK5 Complex Involved in Cell Growth and Migration

Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression

The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination

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