Bag-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway

Michael Witcher, Xiaolong Yang, Alan Pater, Shou-Ching Tang

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Human BAG-1 is an anti-apoptotic protein with four protein isoforms (BAG-1 p50, p46, p33, and p29). BAG-1 p46 was originally isolated in a screen for proteins binding to the glucocorticoid receptor; it binds and modulates the action of several members of the nuclear steroid hormone receptor superfamily. The vitamin D receptor (VDR) is another member of this superfamily, and the vitamin D pathway is important for prevention and therapy of osteoporosis, renal failure, cancer, and psoriasis. Therefore, we investigated the effect of the recently isolated BAG-1 p50 on the vitamin D pathway. By use of Far Western blot analysis and glutathione S-transferase BAG-1 p50 binding assays, BAG-1 p50 was demonstrated to interact with the VDR, and the BAG-1 p50 N-terminus was required. In U87 cells that were stably transfected with BAG-1 p50, binding of the VDR to its response element in electrophoretic mobility shift assays was blocked, enhancement of transcriptional activation was inhibited, cell growth rate was enhanced, cell growth inhibition induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was blocked, and 1,25(OH)2D3-mediated VDR induction was inhibited. These results suggest that BAG-1 p50 is a novel regulator of the vitamin D signaling pathway, and its overexpression may lead to cellular resistance to 1,25(OH)2D3 therapy.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalExperimental Cell Research
Volume265
Issue number1
DOIs
StatePublished - Apr 15 2001

Fingerprint

Calcitriol Receptors
Vitamin D
Protein Isoforms
Far-Western Blotting
Apoptosis Regulatory Proteins
Calcitriol
Steroid Receptors
Kidney Neoplasms
Glucocorticoid Receptors
Response Elements
Electrophoretic Mobility Shift Assay
Cytoplasmic and Nuclear Receptors
Growth
Glutathione Transferase
Psoriasis
Protein Binding
Transcriptional Activation
Osteoporosis
Renal Insufficiency
Therapeutics

Keywords

  • BAG-1 p50 isoform
  • Binding
  • Cell growth
  • U87 glioblastoma cells
  • Vitamin D
  • Vitamin D receptor

ASJC Scopus subject areas

  • Cell Biology

Cite this

Bag-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway. / Witcher, Michael; Yang, Xiaolong; Pater, Alan; Tang, Shou-Ching.

In: Experimental Cell Research, Vol. 265, No. 1, 15.04.2001, p. 167-173.

Research output: Contribution to journalArticle

Witcher, Michael ; Yang, Xiaolong ; Pater, Alan ; Tang, Shou-Ching. / Bag-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway. In: Experimental Cell Research. 2001 ; Vol. 265, No. 1. pp. 167-173.
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