Functional four-base A/T gap core sequence CATTAG of P53 response elements specifically bound tetrameric P53 differently than two-base A/T gap core sequence CATG bound both dimeric and tetrameric P53.
The consensus sequence of p53 is repeated half sites of PuPuPuC(A/T)(A/T)GPyPyPy. GtAGCAttAGCCCAGACATGTCC is a 14-3-3sigma promoter p53 regulation site; the first core sequence is CAttAG, and the second is CATG. Both mutants GtAGgAttAGCCCAGACATGTCC and GtAGCAttAGCCCAGACATcTCC can be activated by p53 as a 1.5-fold half site. The original p53 regulated site on the 14-3-3sigma promoter is a whole site, and CATTAG is a functional core sequence. The p53-binding affinity and the activity of CATTAG were lower than for the mutant CATATG core sequence. Wild-type p53 acts as a tetramer to bind to the whole site; however, it also can bind to a half site by one of its dimers. Wild-type p53 can only bind to a half site with core sequence CATG but not to CATATG. The 1.5-fold half site or whole site with core sequence CATATG can be bound by wild-type p53. A p53 mutant, A344, forms dimeric p53; it can only bind to CATG, and not to CATATG. Therefore, tetrameric and dimeric p53 can bind to a two-base A/T gap core sequence, but only tetrameric p53 can bind to a four-base A/T gap core sequence.
Cai
Bi-He
BH
National Defense Medical Center, Institute of Life Sciences, Taipei, Taiwan, ROC.
Chen
Jang-Yi
JY
Lu
Mei-Hua
MH
Chang
Li-Tze
LT
Lin
Hwang-Chi
HC
Chang
Yu-Ming
YM
Chao
Chung-Faye
CF
D048948:14-3-3 Proteins / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016384:Consensus Sequence; D006801:Humans; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization; D020218:Response Elements; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
D048948:14-3-3 Proteins; D016159:Tumor Suppressor Protein p53