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PMID:17696781

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Citation

Jambunathan, S and Fontes, JD (2007) Sumoylation of the zinc finger protein ZXDC enhances the function of its transcriptional activation domain. Biol. Chem. 388:965-72

Abstract

The transcription of major histocompatibility complex class II (MHC II) genes is dependent on the co-activator protein class II trans-activator (CIITA). We have recently identified a protein known as zinc finger X-linked duplicated family member C (ZXDC) that, along with its binding partner ZXDA, forms a complex that interacts with CIITA and regulates MHC II transcription. Western blot analysis with anti-ZXDC antibodies identified two species of the ZXDC protein, one migrating near its predicted molecular mass and one with slower electrophoretic mobility. We report here that the slower migrating form is the result of sumoylation at a single lysine residue within the transcriptional activation domain of ZXDC. Three SUMO proteins (SUMO-1, -2 and -3) can modify the ZXDC protein. Multiple SUMO E3 ligase enzymes and HDAC4 can facilitate ZXDC sumoylation, and one ligase, PIASy, interacts with a specific region of the ZXDC protein. We found that sumoylation does not appear to disrupt or modulate the interaction of ZXDC with its binding partners. Rather, sumoylation of ZXDC is required for full activity of the transcriptional activation domain. Our findings suggest that sumoylation is an important regulator of ZXDC.

Links

PubMed Online version:10.1515/BC.2007.106

Keywords

Cell Line, Tumor; Gene Expression Regulation; Histocompatibility Antigens Class II/immunology; Histocompatibility Antigens Class II/metabolism; Humans; Protein Structure, Tertiary; Small Ubiquitin-Related Modifier Proteins/metabolism; Trans-Activators/chemistry; Trans-Activators/metabolism; Transcription Factors/metabolism; Transcriptional Activation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PIAS1

involved_in

GO:0033235: positive regulation of protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SUMO3

involved_in

GO:0016925: protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HDAC4

involved_in

GO:0033235: positive regulation of protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SUMO1

involved_in

GO:0016925: protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ZXDA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q2QGD7

F

Seeded From UniProt

complete

HUMAN:ZXDC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8N2W9

F

Seeded From UniProt

complete

HUMAN:ZXDC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P98168

F

Seeded From UniProt

complete

HUMAN:ZXDC

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PIAS4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q2QGD7

F

Seeded From UniProt

complete

HUMAN:PIAS4

involved_in

GO:0033235: positive regulation of protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PIAS3

involved_in

GO:0033235: positive regulation of protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SUMO2

involved_in

GO:0016925: protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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