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>