Calmodulin-driven nuclear entry: trigger for sex determination and terminal differentiation.
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.
Hanover
John A
JA
Laboratory of Cell Biochemistry and Biology, NIDDK, NIH, Bethesda, MD 20892, USA. jah@helix.nih.gov
Love
Dona C
DC
Prinz
William A
WA
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D019849:Sex Determination Processes; D012733:Sex Differentiation; D014157:Transcription Factors
D002147:Calmodulin; D019913:Nuclear Localization Signals; D014157:Transcription Factors