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Calmodulin-driven nuclear entry: trigger for sex determination and terminal differentiation.

ABSTRACT: We originally proposed that Ca(2+)-calmodulin mediates a novel nuclear entry pathway distinct from the canonic Ran-dependent pathway (Sweitzer, T. D., and Hanover, J. A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 14574-14579). Although seemingly redundant, Ca(2+)-calmodulin-driven nuclear entry is now known to facilitate nuclear delivery of architectural transcription factors to chromatin. Intriguingly, defects in calmodulin-driven nuclear import of the transcription factors SRY and SOX9 in Sertoli cells lead to human sex reversal diseases with altered male gonad development. Calmodulin-triggered nuclear entry is an evolutionarily ancient feature of eukaryotes observed from yeast to man. Ca(2+)-calmodulin-triggered nuclear entry of key architectural transcription factors is a potentially key epigenetic regulator of terminal differentiation in response to cell signaling.

SUBMITTER: Hanover JA

PROVIDER: S-EPMC2675987 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Calmodulin-driven nuclear entry: trigger for sex determination and terminal differentiation.

Hanover John A JA Love Dona C DC Prinz William A WA

The Journal of biological chemistry 20090105 19

We originally proposed that Ca(2+)-calmodulin mediates a novel nuclear entry pathway distinct from the canonic Ran-dependent pathway (Sweitzer, T. D., and Hanover, J. A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 14574-14579). Although seemingly redundant, Ca(2+)-calmodulin-driven nuclear entry is now known to facilitate nuclear delivery of architectural transcription factors to chromatin. Intriguingly, defects in calmodulin-driven nuclear import of the transcription factors SRY and SOX9 in Sert ...[more]

PMID: 19126540

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