zinc finger protein PLAG1 (pleiomorphic adenoma gene 1 protein, PLAG1, SGPA)

Function

• transcription factor
• activation results in up-regulation of target genes, including as IGF2, enhancing cell proliferation
• when overexpressed in cultured cells, promotes proliferation & transformation
• other target genes including as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction
• interacts with KPNA2, which escorts PLAG1 to the nucleus via interaction with nuclear localization signal
• interacts with E3 SUMO-protein ligase PIAS1, PIAS2 & PIAS4
• sumoylated by SUMO1 which inhibits transcriptional activity, but does not affect nuclear localization.
  • blockers of sumoylation pathway including as SENP3 & inactive UBE2I increase transcriptional activity of PLAG1
  • sumoylation is increased in the presence of PIAS1
• acetylated by lysine acetyltransferase EP300, which activates transcriptional activity of PLAG1
  • Lys that are sumoylated also seem to be targets for acetylation

Structure

• belongs to the krueppel C2H2-type zinc-finger protein family
• contains 7 C2H2-type zinc fingers C2H2-type zinc fingers 6 & 7 interact with DNA-binding site core sequence
• zinc finger domains confer residual nuclear import after mutation of the nuclear localization signal

Compartment

• nucleus.
• strong nucleolar localization when sumoylation is inhibited

Expression

• expressed in fetal tissues including as lung, liver & kidney
• not detected or weak detection in normal adult tissues

Pathology

• ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland & lipoblastomas
• overexpression is frequently observed in hepatoblastoma
• cooperates with CBFB-MYH11, a fusion gene found in patients with myeloid leukemia
• highly expressed in salivary gland with benign or malignant pleiomorphic adenomas with or without 8q12 abberations, with preferential occurrence in benign tumors
• chromosomal translocation t(3;8)(p21;q12) involving PLAG1 with constituvely expressed beta-catenin/CTNNB1 may be a cause of salivary gland pleiomorphic adenomas
• Ectopic expression of PLAG1 under the control of promoters of distinct translocation partner genes is a general pathogenetic mechanism for pleiomorphic adenomas with 8q aberrations. These fusion genes are likely to be found in adenomas with normal karyotype as this subgroup of tumors also exhibit PLAG1 activation
• chromosomal rearrangement involving PLAG1 may be a cause of lipoblastomas
• chromosomal translocation t(7;8)(p22;q13) invovling PLAG1 with collagen 1A2/COL1A2. Fusion transcript COL1A2-PLAG1 as well as HAS2-PLAG1 encode a full-length PLAG1 protein
• chromosomal translocations t(5;8)(p13;q12) & t(6;8)(p21.3-22;q13) involving PLAG1
• when cultured cells transformed by PLAG1 overexpression are injected in nude mouse, rapidly growing tumors (fibrosarcomas) are observed at the site of inoculation

More general terms

• C2H2 type zinc finger protein
• transcription factor (TF)

Database

• OMIM: https://mirror.omim.org/entry/181030
• OMIM: https://mirror.omim.org/entry/603026
• UniProt: http://www.uniprot.org/uniprot/Q6DJT9.html