PMID- 10646861
OWN - NLM
STAT- MEDLINE
DCOM- 20000204
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 60
IP  - 1
DP  - 2000 Jan 1
TI  - PLAG1, the main translocation target in pleomorphic adenoma of the salivary
      glands, is a positive regulator of IGF-II.
PG  - 106-13
AB  - PLAG1, a novel developmentally regulated C2H2 zinc finger gene, is consistently
      rearranged and overexpressed in pleomorphic adenomas of the salivary glands with 
      8q12 translocations. In this report, we show that PLAG1 is a nuclear protein that
      binds DNA in a specific manner. The consensus PLAG1 binding site is a bipartite
      element containing a core sequence, GRGGC, and a G-cluster, RGGK, separated by
      seven random nucleotides. DNA binding is mediated mainly via three of the seven
      zinc fingers, with fingers 6 and 7 interacting with the core and finger 3 with
      the G-cluster. In transient transactivation assays, PLAG1 specifically activates 
      transcription from its consensus DNA binding site, indicating that PLAG1 is a
      genuine transcription factor. Potential PLAG1 binding sites were found in the
      promoter 3 of the human insulin-like growth factor II (IGF-II) gene. We show that
      PLAG1 binds IGF-II promoter 3 and stimulates its activity. Moreover, IGF-II
      transcripts derived from the P3 promoter are highly expressed in salivary gland
      adenomas overexpressing PLAG1. In contrast, they are not detectable in adenomas
      without abnormal PLAG1 expression nor in normal salivary gland tissue. This
      indicates a perfect correlation between PLAG1 and IGF-II expression. All of these
      results strongly suggest that IGF-II is one of the PLAG1 target genes, providing 
      us with the first clue for understanding the role of PLAG1 in salivary gland
      tumor development.
FAU - Voz, M L
AU  - Voz ML
AD  - Laboratory for Molecular Oncology, Center for Human Genetics, University of
      Leuven, Belgium. marianne.voz@med.kuleuven.ac.be
FAU - Agten, N S
AU  - Agten NS
FAU - Van de Ven, W J
AU  - Van de Ven WJ
FAU - Kas, K
AU  - Kas K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PLAG1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
SB  - IM
MH  - Adenoma, Pleomorphic/*metabolism
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - COS Cells
MH  - DNA-Binding Proteins/chemistry/genetics/*metabolism/physiology
MH  - Humans
MH  - Insulin-Like Growth Factor II/*metabolism
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/chemistry/genetics/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Salivary Gland Neoplasms/*metabolism
MH  - Salivary Glands/*metabolism
MH  - Transcription Factors/chemistry/genetics/physiology
MH  - Up-Regulation
MH  - Zinc Fingers
EDAT- 2000/01/26 00:00
MHDA- 2000/01/26 00:01
CRDT- 2000/01/26 00:00
PHST- 2000/01/26 00:00 [pubmed]
PHST- 2000/01/26 00:01 [medline]
PHST- 2000/01/26 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2000 Jan 1;60(1):106-13.