总苞素
生物
GDF15型
角质形成细胞
哈卡特
细胞分化
细胞生物学
基因敲除
转录因子
内生
分子生物学
细胞培养
遗传学
内分泌学
基因
作者
Tomoe Ichikawa,Yusuke Suenaga,Tadayuki Koda,Toshinori Ozaki,Akira Nakagawara
出处
期刊:Oncogene
[Springer Nature]
日期:2007-07-16
卷期号:27 (4): 409-420
被引量:33
标识
DOI:10.1038/sj.onc.1210658
摘要
Since p63-deficient mice display severe defects in formation of epidermis, p63 has been considered to be a multi-isoform p53 family member essential for epidermal development. However, it is still unclear how p63 could contribute to keratinocyte differentiation. In the present study, we have found that TAp63α is induced in association with the upregulation and a secretion of growth differentiation factor 15 (GDF15) during the keratinocyte differentiation of HaCaT cells bearing p53 mutation. Short interference RNA-mediated knockdown of the endogenous TAp63 resulted in a remarkable reduction of GDF15. Luciferase reporter assay and reverse transcription–PCR analysis demonstrated that enforced expression of TAp63α significantly increases the luciferase activity driven by GDF15 promoter and the expression of GDF15. Consistent with these results, the proximal p53/p63-binding site within the GDF15 promoter region was required for the TAp63α-mediated transcriptional activation of GDF15, and TAp63α was recruited onto this site. Furthermore, siRNA-mediated knockdown of the endogenous GDF15 permitted cell growth and inhibited the expression of the differentiation markers such as keratin 10 and involucrin in response to differentiation stimuli. Taken together, our present results provide a novel insight into understanding the molecular mechanisms behind TAp63α-mediated keratinocyte differentiation.
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