Cyclin-dependent kinase 5 modulates the transcriptional activity of the mineralocorticoid receptor and regulates expression of brain-derived neurotrophic factor

Tomoshige Kino, Howard Jaffe, Niranjana D. Amin, Mayukh Chakrabarti, Ya L. Zheng, George P. Chrousos, Harish C. Pant

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Glucocorticoids, major end effectors of the stress response, play an essential role in the homeostasis of the central nervous system (CNS) and contribute to memory consolidation and emotional control through their intracellular receptors, the glucocorticoid and mineralocorticoid receptors. Cyclin-dependent kinase 5 (CDK5), on the other hand, plays important roles in the morphogenesis and functions of the central nervous system, and its aberrant activation has been associated with development of neurodegenerative disorders. We previously reported that CDK5 phosphorylated the glucocorticoid receptor and modulated its transcriptional activity. Here we found that CDK5 also regulated mineralocorticoid receptor-induced transcriptional activity by phosphorylating multiple serine and threonine residues located in its N-terminal domain through physical interaction. Aldosterone and dexamethasone, respectively, increased and suppressed mRNA/protein expression of brain-derived neurotrophic factor (BDNF) in rat cortical neuronal cells, whereas the endogenous glucocorticoid corticosterone showed a biphasic effect. CDK5 enhanced the effect of aldosterone and dexamethasone on BDNF expression. Because this neurotrophic factor plays critical roles in neuronal viability, synaptic plasticity, consolidation of memory, and emotional changes, we suggest that aberrant activation of CDK5 might influence these functions through corticosteroid receptors/BDNF.

Original languageEnglish
Pages (from-to)941-952
Number of pages12
JournalMolecular Endocrinology
Volume24
Issue number5
DOIs
Publication statusPublished - May 2010
Externally publishedYes

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Cyclin-Dependent Kinase 5
Mineralocorticoid Receptors
Brain-Derived Neurotrophic Factor
Glucocorticoid Receptors
Aldosterone
Dexamethasone
Glucocorticoids
Central Nervous System
Neuronal Plasticity
Steroid Receptors
Nerve Growth Factors
Threonine
Corticosterone
Morphogenesis
Neurodegenerative Diseases
Serine
Homeostasis
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology

Cite this

Cyclin-dependent kinase 5 modulates the transcriptional activity of the mineralocorticoid receptor and regulates expression of brain-derived neurotrophic factor. / Kino, Tomoshige; Jaffe, Howard; Amin, Niranjana D.; Chakrabarti, Mayukh; Zheng, Ya L.; Chrousos, George P.; Pant, Harish C.

In: Molecular Endocrinology, Vol. 24, No. 5, 05.2010, p. 941-952.

Research output: Contribution to journalArticle

Kino, Tomoshige ; Jaffe, Howard ; Amin, Niranjana D. ; Chakrabarti, Mayukh ; Zheng, Ya L. ; Chrousos, George P. ; Pant, Harish C. / Cyclin-dependent kinase 5 modulates the transcriptional activity of the mineralocorticoid receptor and regulates expression of brain-derived neurotrophic factor. In: Molecular Endocrinology. 2010 ; Vol. 24, No. 5. pp. 941-952.
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