PLAG1

Pleomorphic adenoma gene 1 encodes a zinc finger protein with 2 putative nuclear localization signals. PLAG1, which is developmentally regulated, has been shown to be consistently rearranged in pleomorphic adenomas of the salivary glands. PLAG1 is activated by the reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq]

Full Name

PLAG1

Function

Transcription factor whose activation results in up-regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Overexpression is associated with up-regulation of IGFII, is frequently observed in hepatoblastoma, common primary liver tumor in childhood. Cooperates with CBFB-MYH11, a fusion gene important for myeloid leukemia.

Biological Process

Gland morphogenesisIEA:Ensembl
Multicellular organism growthIEA:Ensembl
Negative regulation of gene expressionIEA:Ensembl
Positive regulation of gene expressionIEA:Ensembl
Positive regulation of glial cell proliferationIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:NTNU_SB
Prostate gland growthIEA:Ensembl
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIBA:GO_Central
Transcription, DNA-templatedIEA:InterPro

Cellular Location

Nucleus
Strong nucleolar localization when sumoylation is inhibited.

Involvement in disease

Silver-Russell syndrome 4 (SRS4):
A form of Silver-Russell syndrome, a clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. SRS4 inheritance is autosomal dominant.

PTM

Sumoylated with SUMO1; which inhibits transcriptional activity, but does not affect nuclear localization. Blockers of sumoylation pathway such as SENP3 and inactive UBE2I increases transcriptional capacity. Sumoylation is increased in the presence of PIAS1.
Acetylated by lysine acetyltransferase EP300; which activates transcriptional capacity. Lysine residues that are sumoylated also seem to be target for acetylation.