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2015 ; 58
(5
): 743-54
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Cancer/Testis Antigen PASD1 Silences the Circadian Clock
#MMPMID25936801
Michael AK
; Harvey SL
; Sammons PJ
; Anderson AP
; Kopalle HM
; Banham AH
; Partch CL
Mol Cell
2015[Jun]; 58
(5
): 743-54
PMID25936801
show ga
The circadian clock orchestrates global changes in transcriptional regulation on
a daily basis via the bHLH-PAS transcription factor CLOCK:BMAL1. Pathways driven
by other bHLH-PAS transcription factors have a homologous repressor that
modulates activity on a tissue-specific basis, but none have been identified for
CLOCK:BMAL1. We show here that the cancer/testis antigen PASD1 fulfills this role
to suppress circadian rhythms. PASD1 is evolutionarily related to CLOCK and
interacts with the CLOCK:BMAL1 complex to repress transcriptional activation.
Expression of PASD1 is restricted to germline tissues in healthy individuals but
can be induced in cells of somatic origin upon oncogenic transformation. Reducing
PASD1 in human cancer cells significantly increases the amplitude of
transcriptional oscillations to generate more robust circadian rhythms. Our
results describe a function for a germline-specific protein in regulation of the
circadian clock and provide a molecular link from oncogenic transformation to
suppression of circadian rhythms.