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PMID:17223341

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Citation

Oda, Y, Ishikawa, MH, Hawker, NP, Yun, QC and Bikle, DD (2007) Differential role of two VDR coactivators, DRIP205 and SRC-3, in keratinocyte proliferation and differentiation. J. Steroid Biochem. Mol. Biol. 103:776-80

Abstract

Cell programs such as proliferation and differentiation involve the selective activation and repression of gene expression. The vitamin D receptor (VDR), through 1,25(OH)(2)D(3), controls the proliferation and differentiation of keratinocytes. Previously, we have identified two VDR binding coactivator complexes. In proliferating keratinocytes VDR bound preferentially to the DRIP complex, whereas in differentiated keratinocytes the SRC complex was preferred. We proposed that different coactivators are required for sequential gene regulation in the transition from proliferation to differentiation. Here we examined the roles of DRIP205 and SRC-3 in this transition. Silencing of DRIP205 and VDR caused hyperproliferation of keratinocytes, demonstrated by increased XTT and BrdU incorporation. SRC-3 silencing, on the other hand, did not have an effect on proliferation. In contrast, SRC-3 as well as DRIP205 and VDR silencing blocked keratinocyte differentiation as shown by decreased expression of keratin 1 and filaggrin. These results are consistent with the differential localization of DRIP205 and SRC-3 in skin. These results indicate that DRIP205 is required for keratinocyte proliferation. Both DRIP205 and SRC-3 are required for the keratinocyte differentiation. These results support the concept that the selective use of coactivators by VDR underlies the selective regulation of gene expression in keratinocyte proliferation and differentiation.

Links

PubMed Online version:10.1016/j.jsbmb.2006.12.069

Keywords

Cell Differentiation; Cell Proliferation; Cells, Cultured; Histone Acetyltransferases/genetics; Histone Acetyltransferases/metabolism; Humans; Keratinocytes/cytology; Keratinocytes/metabolism; Mediator Complex Subunit 1; Nuclear Receptor Coactivator 3; RNA, Small Interfering/genetics; Receptors, Calcitriol/metabolism; Trans-Activators/genetics; Trans-Activators/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

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

HUMAN:VDR

involved_in

GO:0000902: cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

HUMAN:VDR

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P04264)|has_input:(UniProtKB:P20930)

Seeded From UniProt

complete

HUMAN:MED1

involved_in

GO:0030216: keratinocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MED1

involved_in

GO:0000902: cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

HUMAN:MED1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000312)

Seeded From UniProt

complete

HUMAN:MED1

involved_in

GO:0010839: negative regulation of keratinocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MED1

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P20930)

Seeded From UniProt

complete

HUMAN:MED1

enables

GO:0003713: transcription coactivator activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MED1

enables

GO:0042809: vitamin D receptor binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MED1

involved_in

GO:2001141: regulation of RNA biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NCOA3

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NCOA3

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000312)

Seeded From UniProt

complete

HUMAN:NCOA3

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000312)

Seeded From UniProt

complete

HUMAN:NCOA3

enables

GO:0003713: transcription coactivator activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NCOA3

involved_in

GO:0045618: positive regulation of keratinocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NCOA3

involved_in

GO:0035624: receptor transactivation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VDR

involved_in

GO:0010839: negative regulation of keratinocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VDR

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P04264)|has_regulation_target:(UniProtKB:P20930)

Seeded From UniProt

complete

HUMAN:VDR

involved_in

GO:0000902: cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000312)

Seeded From UniProt

complete


See also

References

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