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Beschreibung

Circadian clock protein PASD1 (UniProt: Q8IV76, also known as Cancer/testis antigen 63, CT63, OC-TES 11, PAS domain-containing protein 1) is encoded by the PASD1 gene (Gene ID: 139135) in human. PASD1 is evolutionarily nuclear protein that associates preferentially at the periphery of the nucleus with heterochromatin. Human PASD1 contains an N-terminal PAS domain (a.a. 30-102), a central region (a.a. 365-412) essential for its transcriptional repression activity, and two coiled coil domains (CC1/a.a. 365-412 and CC2/a.a. 475-553), where CC1 exhibits significant homology with CLOCK exon 19-coded sequence. PASD1 is related to CLOCK and interacts with the bHLH-PAS transcription complex CLOCK-BMAL1 to repress transcriptional activation. PASD1 expression is normally limited to immunologically restricted germline tissues that do not express class I MHC molecules, such as testis and placenta, allowing tissue-specific circadian rhythms suppression. It is also expressed in a broad range of cancer cells, including melanoma, lung cancer, and breast cancer. It displays widespread expression in solid tumors and diffuse large B-cell lymphoma (DLBCL)-derived cell lines. Isoform 2 is expressed in all DLBCL-derived cell lines, while isoform 1 is preferentially expressed in cell lines derived from non-germinal center DLBCL. When over-expressed, PASD1 inhibits circadian clock function in cancer cells and reducing PASD1 in cancer cells significantly increases the amplitude of transcriptional oscillations to generate more robust circadian rhythms.