Synergistic efficacy of LBH and alphaB-crystallin through inhibiting transcriptional activities of p53 and p21.
LBH is a transcription factor as a candidate gene for CHD associated with partial trisomy 2p syndrome. To identify potential LBH-interacting partners, a yeast two-hybrid screen using LBH as a bait was performed with a human heart cDNA library. One of the clones identified encodes alphaB-crystallin. Co-immunoprecipitation and GST pull-down assays showed that LBH interacts with alphaB-crystallin, which is further confirmed by mammalian two-hybrid assays. Co-localization analysis showed that in COS-7 cells, alphaB-crystallin that is cytoplasmic alone, accumulates partialy in the nucleus when co-transfected with LBH. Transient transfection assays indicated that overexpression of LBH or alphaB-crystallin reduced the transcriptional activities of p53 and p21, respectively, Overexpression of both alphaB-crystallin and LBH together resulted in a stronger repression of the transcriptional activities of p21 and p53. These results showed that the interaction of LBH and alphaB-crystallin may inhibit synergistically the transcriptional regulation of p53 and p21.
Deng
Yun
Y
The Center For Heart Development, Hunan Normal University, Changsha, Hunan, Peoples' Republic of China.
Li
Yongqing
Y
Fan
Xiongwei
X
Yuan
Wuzhou
W
Xie
Huaping
H
Mo
Xiaoyang
X
Yan
Yan
Y
Zhou
Junmei
J
Wang
Yuequn
Y
Ye
Xianli
X
Wan
Yongqi
Y
Wu
Xiushan
X
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003459:Crystallins / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D015689:Oncogene Protein p21(ras) / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D003459:Crystallins; C531176:LBH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D015689:Oncogene Protein p21(ras)