The tumour suppressor p53 transactivates the expression of its target genes to exert its functions. Here, we identify a pleckstrin homology domain-containing protein (PHLDB3)encoding gene as a p53 target. PHLDB3 overexpression increases proliferation and restrains apoptosis of wild-type p53-harboring cancer cells by reducing p53 protein levels. PHLDB3 binds to MDM2 (mouse double minute 2 homolog) and facilitates MDM2-mediated ubiquitination and degradation of p53. Knockdown of PHLDB3 more efficiently inhibits the growth of mouse xenograft tumours derived from human colon cancer HCT116 cells that contain wild type p53 compared with p53-deficient HCT116 cells, and also sensitizes tumour cells to doxorubicin and 5-Fluorouracil. Analysis of cancer genomic databases reveals that PHLDB3 is amplified and/or highly expressed in numerous human cancers. Altogether, these results demonstrate that PHLDB3 promotes tumour growth by inactivating p53 in a negative feedback fashion and suggest PHLDB3 as a potential therapeutic target in various human cancers.
基金：
NIH-NCI [R01CA095441, R01CA172468, R01CA127724, R21CA190775, R21CA201889]; Reynolds and Ryan Families Chair fund; National Natural Science Foundation of China [81201820]
第一作者单位：[1]Tulane Univ, Sch Med, Dept Biochem & Mol Biol, 1430 Tulane Ave, New Orleans, LA 70112 USA[2]Tulane Univ, Sch Med, Tulane Canc Ctr, 1430 Tulane Ave, New Orleans, LA 70112 USA[3]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Oncol, Wuhan 430030, Peoples R China
通讯作者：
通讯机构：[1]Tulane Univ, Sch Med, Dept Biochem & Mol Biol, 1430 Tulane Ave, New Orleans, LA 70112 USA[2]Tulane Univ, Sch Med, Tulane Canc Ctr, 1430 Tulane Ave, New Orleans, LA 70112 USA[6]Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA
推荐引用方式(GB/T 7714)：
Chao Tengfei,Zhou Xiang,Cao Bo,et al.Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53[J].NATURE COMMUNICATIONS.2016,7:doi:10.1038/ncomms13755.
APA：
Chao, Tengfei,Zhou, Xiang,Cao, Bo,Liao, Peng,Liu, Hongbing...&Lu, Hua.(2016).Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53.NATURE COMMUNICATIONS,7,
MLA：
Chao, Tengfei,et al."Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53".NATURE COMMUNICATIONS 7.(2016)
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