Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1029-1040 ◽  
Author(s):  
L.H. Tsai ◽  
T. Takahashi ◽  
V.S. Caviness ◽  
E. Harlow
Keyword(s):  
Nervous System ◽  
Cell Division ◽  
Cell Division Cycle ◽  
Adult Brain ◽  
Cyclin Dependent Kinase ◽  
Proliferating Cells ◽  
Embryonic Mouse ◽  
Postmitotic Neurons ◽  
Cyclin Dependent Kinase 5 ◽  
Expression And Activity

Cyclin-dependent kinase 5 (cdk5) was originally isolated on the basis of its close primary sequence homology to the human cdc2 serine/threonine kinase, the prototype of the cyclin-dependent kinases. While kinase activities of both cdc2 and cdk2 are detected in proliferating cells and are essential for cells to progress through the key transition points of the cell cycle, cdk5 kinase activity has been observed only in lysates of adult brain. In this study, we compared the activity and expression of cdk5 with that of cdc2 and cdk2 in the embryonic mouse forebrain. The expression and activity of cdk5 increased progressively as increasing numbers of cells exited the proliferative cycle. In contrast, the expression and activity of cdc2 and cdk2 were maximum at gestational day 11 (E11) when the majority of cells were proliferating and fell to barely detectable levels at E17 at the end of the cytogenetic period. Immunohistochemical studies showed that cdk5 is expressed in postmitotic neurons but not in glial cells or mitotically active cells. Expression of cdk5 was concentrated in fasciculated axons of postmitotic neurons. In contrast to other cell division cycle kinases to which it is closely related, cdk5 appears not to be expressed in dividing cells in the developing brain. These observations suggest that cdk5 may have a role in neuronal differentiation but not in the cell division cycle in the embryonic nervous system.

scholarly journals Expression and Activity of Cyclin-Dependent Kinase 5/p35 in Adult Rat Peripheral Nervous System

2002 ◽  
Vol 71 (6) ◽  
pp. 2600-2606 ◽  
Author(s):  
Masahiko Terada ◽  
Hitoshi Yasuda ◽  
Syuro Kogawa ◽  
Kengo Maeda ◽  
Masakazu Haneda ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Cyclin Dependent Kinase ◽  
Adult Rat ◽  
Cyclin Dependent Kinase 5 ◽  
Expression And Activity

scholarly journals p12DOC-1 Is a Novel Cyclin-Dependent Kinase 2-Associated Protein

2000 ◽  
Vol 20 (17) ◽  
pp. 6300-6307 ◽  
Author(s):  
Satoru Shintani ◽  
Hiroe Ohyama ◽  
Xue Zhang ◽  
Jim McBride ◽  
Kou Matsuo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Ectopic Expression ◽  
Cell Division Cycle ◽  
Cyclin Dependent Kinase ◽  
Data Support ◽  
Normal Keratinocytes ◽  
Active Pool ◽  
Growth Suppressor

ABSTRACT Regulated cyclin-dependent kinase (CDK) levels and activities are critical for the proper progression of the cell division cycle. p12DOC-1 is a growth suppressor isolated from normal keratinocytes. We report that p12DOC-1 associates with CDK2. More specifically, p12DOC-1 associates with the monomeric nonphosphorylated form of CDK2 (p33CDK2). Ectopic expression of p12DOC-1 resulted in decreased cellular CDK2 and reduced CDK2-associated kinase activities and was accompanied by a shift in the cell cycle positions of p12DOC-1transfectants (↑ G1 and ↓ S). The p12DOC-1-mediated decrease of CDK2 was prevented if the p12DOC-1 transfectants were grown in the presence of the proteosome inhibitor clasto-lactacystin β-lactone, suggesting that p12DOC-1 may target CDK2 for proteolysis. A CDK2 binding mutant was created and was found to revert p12DOC-1-mediated, CDK2-associated cell cycle phenotypes. These data support p12DOC-1 as a specific CDK2-associated protein that negatively regulates CDK2 activities by sequestering the monomeric pool of CDK2 and/or targets CDK2 for proteolysis, reducing the active pool of CDK2.

scholarly journals Activation of Cyclin-Dependent Kinase 5 Is a Consequence of Cell Death

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Yixia Ye ◽  
Antonella Tinari ◽  
Walter Malorni ◽  
Richard A. Lockshin ◽  
Zahra Zakeri
Keyword(s):  
Cell Death ◽  
Cell Division ◽  
Cell Differentiation ◽  
Metabolic Changes ◽  
Cyclin Dependent Kinase ◽  
Secondary Necrosis ◽  
Kinetics Of ◽  
Cyclin Dependent Kinase 5

Cyclin-dependent kinase 5 (Cdk5) is similar to other Cdks but is activated during cell differentiation and cell death rather than cell division. Since activation of Cdk5 has been reported in many situations leading to cell death, we attempted to determine if it was required for any form of cell death. We found that Cdk5 is activated during apoptotic deaths and that the activation can be detected even when the cells continue to secondary necrosis. This activation can occur in the absence of Bim, calpain, or neutral cathepsins. The kinase is typically activated by p25, derived from p35 by calpain-mediated cleavage, but inhibition of calpain does not affect cell death or the activation of Cdk5. Likewise, RNAi-forced suppression of the synthesis of Cdk5 does not affect the incidence or kinetics of cell death. We conclude that Cdk5 is activated as a consequence of metabolic changes that are common to many forms of cell death. Thus its activation suggests processes during cell death that will be interesting or important to understand, but activation of Cdk5 is not necessary for cells to die.

scholarly journals Tissue-specific expression of the heat shock protein HSP27 during Drosophila melanogaster development.

1990 ◽  
Vol 111 (3) ◽  
pp. 817-828 ◽  
Author(s):  
D Pauli ◽  
C H Tonka ◽  
A Tissieres ◽  
A P Arrigo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drosophila Melanogaster ◽  
Heat Shock ◽  
Stress Protein ◽  
Pupal Stage ◽  
Adult Brain ◽  
Proliferating Cells ◽  
Specific Expression ◽  
The Central Nervous System

The alpha-crystallin-related heat shock (stress) protein hsp27 is expressed in absence of heat shock during Drosophila melanogaster development. Here, we describe the tissue distribution of this protein using an immunoaffinity-purified antibody. In embryos, hsp27 translated from maternal RNA is uniformly distributed, except in the yolk. During the first, second, and early third larval stages, hsp27 expression is restricted to the brain and the gonads. These tissues are characterized by a high level of proliferating cells. In late third instar larvae and early pupae, in addition to the central nervous system and the gonads, all the imaginal discs synthesize hsp27. The disc expression seems restricted to the beginning of their differentiation since it disappears during the second half of the pupal stage: no more hsp27 is observed in the disc-derived adult organs. In adults, hsp27 is still present in some regions of the central nervous system, and is also expressed in the male and female germ lines where it accumulates in mature sperm and oocytes. The transcript and the protein accumulate in oocytes since the onset of vitellogenesis with a uniform distribution similar to that found in embryos. The adult germ lines transcribe hsp27 gene while no transcript is detected in the late pupal and adult brain. These results suggest multiple roles of hsp27 during Drosophila development which may be related to both the proliferative and differentiated states of the tissues.

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 Cyclin-Dependent Kinase 5 Differentially Regulates the Transcriptional Activity of the Glucocorticoid Receptor through Phosphorylation: Clinical Implications for the Nervous System Response to Glucocorticoids and Stress

2007 ◽  
Vol 21 (7) ◽  
pp. 1552-1568 ◽  
Author(s):  
Tomoshige Kino ◽  
Takamasa Ichijo ◽  
Niranjana D. Amin ◽  
Sashi Kesavapany ◽  
Yonghong Wang ◽  
...  
Keyword(s):  
Nervous System ◽  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Biological Activities ◽  
Neuronal Cells ◽  
System Response ◽  
Cyclin Dependent Kinase ◽  
Proteolytic Fragment ◽  
End Effectors ◽  
Cyclin Dependent Kinase 5

Abstract Glucocorticoids, major end effectors of the stress response, play an essential role in the homeostasis of the central nervous system and influence diverse functions of neuronal cells. We found that cyclin-dependent kinase 5 (CDK5), which plays important roles in the morphogenesis and functions of the nervous system and whose aberrant activation is associated with development of neurodegenerative disorders, interacted with the ligand-binding domain of the glucocorticoid receptor (GR) through its activator p35 or its active proteolytic fragment p25. CDK5 phosphorylated GR at multiple serines, including Ser203 and Ser211 of its N-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to DNA. In microarray analyses using rat cortical neuronal cells, the CDK5 inhibitor roscovitine differentially regulated the transcriptional activity of the GR on more than 90% of the endogenous glucocorticoid-responsive genes tested. Thus, CDK5 exerts some of its biological activities in neuronal cells through the GR, dynamically modulating GR transcriptional activity in a target promoter-dependent fashion.

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