Cai Bi-He, Chao Chung-Faye, Lin Hwang-Chi, Huang Hua-Ying, Kannagi Reiji, Chen Jang-Yi
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
J Biochem. 2016 Jun;159(6):563-72. doi: 10.1093/jb/mvw005. Epub 2016 Jan 27.
The canonical core sequence of the p53 response element, CATG, has a two-base A/T gap. Previously, we found that p53 can also activate a non-canonical four-base A/T gap CATATG core sequence. In this study, we investigated the possible number of A/T bases used by p53 and showed that a six-base A/T gap CATATATG core sequence was the maximum A/T gap in the p53 response element that could be upregulated by p53 and p63. Canonical and non-canonical p53 response elements also have three-base flanking sequences. A/T bases could be substituted by G/C bases, including CACACG and CGTGTG, but not CGCGCG. We found that the SV40 promoter with functional six- and two-base A/T gap core sequences could be activated by TAp63γ and that TAp63γ could upregulate SV40 small and large T antigens expression in COS7 cells. We also found that the distal region of PUMA promoter with functional two six-base A/T gap core sequences could be activated by TAp63γ in 293T cells. These new findings could provide novel rules for the non-canonical p53 family response element and could extend the entire p53 family regulation network.
p53反应元件的典型核心序列CATG有一个两碱基的A/T间隔。此前，我们发现p53还能激活一个非典型的四碱基A/T间隔CATATG核心序列。在本研究中，我们探究了p53使用的A/T碱基的可能数量，并表明一个六碱基A/T间隔CATATATG核心序列是p53和p63能上调的p53反应元件中的最大A/T间隔。典型和非典型p53反应元件也有三碱基侧翼序列。A/T碱基可被G/C碱基取代，包括CACACG和CGTGTG，但不是CGCGCG。我们发现具有功能性六碱基和两碱基A/T间隔核心序列的SV40启动子可被TAp63γ激活，并且TAp63γ可上调COS7细胞中SV40小T抗原和大T抗原的表达。我们还发现具有功能性两个六碱基A/T间隔核心序列的PUMA启动子远端区域可被293T细胞中的TAp63γ激活。这些新发现可为非典型p53家族反应元件提供新规则，并可扩展整个p53家族调控网络。
