A molecular scaffold HIC-5-and KLF4-dependent mechanism transactivates p21^<Cip1> in response to loss of anchorage

在这项研究中，我们表明，HIC-5也参与转录上调细胞周期蛋白依赖性激酶抑制剂（CKI）p21^<Cip1>在非贴壁细胞，从而有助于生长停滞。p21 α的反式激活<Cip1>在上游元件即转录应答元件（DRE）上受到调控，该元件由Kruppel样KLF 4和Runt相关RUNX 1两个转录因子的结合位点组成，这两个位点对p21 α的反式激活都是必需的，但单独存在并不充分。HIC-5通过促进KLF 4在DNA位点上的拴系过程与其在非粘附条件下增加的核基质定位密切相关，从而关键地参与反式激活。在Runx 1位点，一个LIM-唯一的蛋白质，CRP 2，在粘附条件下施加负调控，这是假定删除后失去锚定，并有助于提高转录活性的DRE协同调节KLF 4网站。总之，这项研究揭示了一种新的转录机制，调节基因的表达，在一个转录依赖的方式。

In this study, we show that HIC-5 is also engaged in transcriptional upregulation of a cyclin-dependent kinase inhibitor(CKI) p21^<Cip1> in non-adherent cells, thereby contributing to the growth arrest. The transactivation of p21^<Cip1> was regulated at the upstream element, designate detachment-responsive element(DRE), consisting of binding sites for the two transcription factors, Kruppel-like KLF4 and runt-related RUNX1 ; Both sites were necessary but not sufficient alone for the transactivation. HIC-5 was critically involved in the transactivation by facilitating the tethering process of KLF4 onto the DNA sites in association with its increased localization to the nuclear matrix under non-adherent conditions. At the Runx1 site, a LIM-only protein, CRP2, imposed negative regulation under adherent conditions, which was assumingly removed upon loss of anchorage and contributed to the elevated transcriptional activity of DRE collaboratively with the regulation at the KLF4 sites. In conclusion, this study uncovered a novel transcriptional mechanism regulating gene expression in a detachment-dependent manner.