AP-2β enhances p53-mediated transcription of the αB-crystallin gene through stabilizing p53
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The αB-crystallin (CRYAB) is a member of the small heat shock protein family that can be induced by various stresses and pathological conditions. Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously. Although the CRYAB promoter contains four consensus binding sequences of AP-2 and can be activated by AP-2α either in the presence or absence of p53, the luciferase assay showed that AP-2β alone does not regulate the activity of the CRYAB promoter in the absence of p53. However, in the presence of p53, AP-2β can significantly increase the luciferase activities of both the CRYAB promoter and reporter vector pp53-TA-luc, which contains a p53-responsive element, but no AP-2 binding sites. These data suggest that AP-2β enhances transactivation of p53 and regulates CRYAB transcription via p53. Further study demonstrated that AP-2β interacts with p53 and augments its protein stability. Taken together, our results indicate that AP-2β up-regulates the transcription of the CRYAB gene through stabilizing p53.
KeywordsAP-2β Tumor suppressor protein p53 αB-crystallin Protein stability
This work was supported by National Natural Science Foundation of China (Grant Nos. 81071656, 31071150 and 30971570).
- 6.Kamradt MC, Lu M, Werner ME, Kwan T, Chen F, Strohecker A, Oshita S, Wilkinson JC, Yu C, Oliver PG, Duckett CS, Buchsbaum DJ, LoBuglio AF, Jordan VC, Cryns VL (2005) The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem 280(12):11059–11066PubMedCrossRefGoogle Scholar
- 12.Lung HL, Lo CC, Wong CC, Cheung AK, Cheong KF, Wong N, Kwong FM, Chan KC, Law EW, Tsao SW, Chua D, Sham JS, Cheng Y, Stanbridge EJ, Robertson GP, Lung ML (2008) Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma. Int J Cancer 122(6):1288–1296PubMedCrossRefGoogle Scholar