PMID- 16501612
OWN - NLM
STAT- MEDLINE
DCOM- 20060523
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 25
IP  - 16
DP  - 2006 Apr 13
TI  - p53 negatively regulates the expression of FAT10, a gene upregulated in various 
      cancers.
PG  - 2318-27
AB  - FAT10 is a member of the ubiquitin-like modifier family of proteins and has been 
      implicated to play important roles in antigen presentation, cytokine response, 
      apoptosis and mitosis. We have recently demonstrated the upregulation of FAT10 
      gene expression in 90% of hepatocellular carcinoma patients. Here, we identified 
      and characterized the promoter of the FAT10 gene to elucidate the mechanism of 
      FAT10 gene expression. Notably, we found that the 5' untranslated region (5'UTR), 
      from the transcription start site to 15 bases before the translational start 
      site, displays significant promoter activity. Regions upstream of the 5'UTR (from 
      +26 to -1997) do not confer any promoter activity. Curiously, FAT10 promoter 
      activity and expression is significantly repressed in KB3-1 and HepG2 cells, 
      which have wild-type p53, than in p53-negative Hep3B cells. The role of p53 in 
      regulating FAT10 expression was evident by the significant downregulation 
      (P<0.05) of FAT10 mRNA expression and promoter activity when wild-type p53 was 
      transfected into p53-null Hep3B cells. Conversely, inhibiting p53 expression 
      through siRNA against p53 significantly enhanced FAT10 expression and promoter 
      activity. p53 was found to bind in vivo to the 5' half consensus sequence of 
      p53-binding site located at the FAT10 promoter. Hence, we propose that FAT10 is a 
      downstream target of p53 and dysregulation of FAT10 expression in p53-defective 
      cells could contribute to carcinogenesis.
FAU - Zhang, D W
AU  - Zhang DW
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore.
FAU - Jeang, K-T
AU  - Jeang KT
FAU - Lee, C G L
AU  - Lee CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (MAD2L1 protein, human)
RN  - 0 (Mad2 Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (UBD protein, human)
RN  - 0 (Ubiquitins)
SB  - IM
MH  - 5' Untranslated Regions/physiology
MH  - Base Sequence
MH  - Binding Sites
MH  - Calcium-Binding Proteins/physiology
MH  - Cell Cycle Proteins/physiology
MH  - Cell Line
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mad2 Proteins
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - RNA, Small Interfering/pharmacology
MH  - Repressor Proteins/physiology
MH  - Tumor Suppressor Protein p53/*physiology
MH  - Ubiquitins/*genetics
MH  - Up-Regulation
EDAT- 2006/02/28 09:00
MHDA- 2006/05/24 09:00
CRDT- 2006/02/28 09:00
PHST- 2006/02/28 09:00 [pubmed]
PHST- 2006/05/24 09:00 [medline]
PHST- 2006/02/28 09:00 [entrez]
AID - 1209220 [pii]
AID - 10.1038/sj.onc.1209220 [doi]
PST - ppublish
SO  - Oncogene. 2006 Apr 13;25(16):2318-27. doi: 10.1038/sj.onc.1209220.