10.6084/m9.figshare.3394531 Rachel Beckerman Rachel Beckerman Kathryn Yoh Kathryn Yoh Melissa Mattia-Sansobrino Melissa Mattia-Sansobrino Andrew Zupnick Andrew Zupnick Oleg Laptenko Oleg Laptenko Orit Karni-Schmidt Orit Karni-Schmidt Jinwoo Ahn Jinwoo Ahn In-Ja Byeon In-Ja Byeon Susan Keezer Susan Keezer Carol Prives Carol Prives Lysines in the tetramerization domain of p53 selectively modulate G1 arrest Taylor & Francis Group 2016 acetylation apoptosis cell cycle tumor suppressor p53 p21 2016-05-21 07:15:27 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Lysines_in_the_tetramerization_domain_of_p53_selectively_modulate_G1_arrest/3394531 <p>Functional in a tetrameric state, the protein product of the <i>p53</i> tumor suppressor gene confers its tumor-suppressive activity by transactivating genes which promote cell-cycle arrest, senescence, or programmed cell death. How p53 distinguishes between these divergent outcomes is still a matter of considerable interest. Here we discuss the impact of 2 mutations in the tetramerization domain that confer unique properties onto p53. By changing lysines 351 and 357 to arginine, thereby blocking all post-translational modifications of these residues, DNA binding and transcriptional regulation by p53 remain virtually unchanged. On the other hand, by changing these lysines to glutamine (2KQ-p53), thereby neutralizing their positive charge and potentially mimicking acetylation, p53 is impaired in the induction of cell cycle arrest and yet can still effectively induce cell death. Surprisingly, when 2KQ-p53 is expressed at high levels in H1299 cells, it can bind to and transactivate numerous p53 target genes including <i>p21</i>, but not others such as <i>miR-34a</i> and <i>cyclin G1</i> to the same extent as wild-type p53. Our findings show that strong induction of p21 is not sufficient to block H1299 cells in G1, and imply that modification of one or both of the lysines within the tetramerization domain may serve as a mechanism to shunt p53 from inducing cell cycle arrest.</p>