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Transcriptional coactivator with PDZ-binding motif is required to sustain testicular function on aging

Title
Transcriptional coactivator with PDZ-binding motif is required to sustain testicular function on aging
Authors
Jeong, Mi GyeongSong, HyunaShin, Ji HyunJeong, HanaKim, Hyo KyeongHwang, Eun Sook
Ewha Authors
황은숙
SCOPUS Author ID
황은숙scopus
Issue Date
2017
Journal Title
AGING CELL
ISSN
1474-9726JCR Link
Citation
vol. 16, no. 5, pp. 1035 - 1042
Keywords
apoptosisfertilityp53-p21senescencesperm countsTAZ deficiency
Publisher
WILEY
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Transcriptional coactivator with PDZ-binding motif (TAZ) directly interacts with transcription factors and regulates their transcriptional activity. Extensive functional studies have shown that TAZ plays critical regulatory roles in stem cell proliferation, differentiation, and survival and also modulates the development of organs such as the lung, kidney, heart, and bone. Despite the importance of TAZ in stem cell maintenance, TAZ function has not yet been evaluated in spermatogenic stem cells of the male reproductive system. Here, we investigated the expression and functions of TAZ in mouse testis. TAZ was expressed in spermatogenic stem cells; however, its deficiency caused significant structural abnormalities, including atrophied tubules, widened interstitial space, and abnormal Leydig cell expansion, thereby resulting in lowered sperm counts and impaired fertility. Furthermore, TAZ deficiency increased the level of apoptosis and senescence in spermatogenic cells and Leydig cells upon aging. The expression of senescence-associated beta-galactosidase (SA-beta gal), secretory phenotypes, and cyclin-dependent kinase inhibitors (p16, p19, and p21) significantly increased in the absence of TAZ. TAZ downregulation in testicular cells further increased SA-beta gal and p21 expression induced by oxidative stress, whereas TAZ overexpression decreased p21 induction and prevented senescence. Mechanistic studies showed that TAZ suppressed DNA-binding activity of p53 through a direct interaction and thus attenuated p53-induced p21 gene transcription. Our results suggested that TAZ may suppress apoptosis and premature senescence in spermatogenic cells by inhibiting the p53-p21 signaling pathway, thus playing important roles in the maintenance and control of reproductive function.
DOI
10.1111/acel.12631
Appears in Collections:
약학대학 > 약학과 > Journal papers
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