Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis

Lee, San San; Crabb, Simon J.; Janghra, Nari; Carlberg, Carsten; Williams, Ann C.; Cutress, Ramsey I.; Packham, Graham; Hague, Angela

doi:10.1016/j.yexcr.2007.06.010

Cited by 12 publications

(15 citation statements)

References 52 publications

(90 reference statements)

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“…Immunoblot analysis showed that the wild type and mutant BAG-1S proteins were expressed at approximately equivalent levels ( Figure 6B). As shown earlier (Briknarova et al, 2001;Townsend et al, 2004;Lee et al, 2007), mutation of helix 2 and 3, but not helix 1, prevented interaction of BAG-1S with HSC70 in co-immunoprecipitation assays ( Figure 8A). …”

Section: Inhibition Of P73a Function By Bag-1s Requires Helix 2 and 3supporting

confidence: 84%

“…Both the ability of BAG-1S to modulate p73a-transcriptional activity and to associate with p73a was dependent on specific residues within the BAG-1 BAG domain that are also required for binding to HSC70 and for promotion of cell survival Lee et al, 2007). The data are consistent with a model in which the binding of BAG-1 to p73a is mediated by HSC70/HSP70, but studies with purified components are required to test this.…”

Section: Bag-1s (G3e2)supporting

confidence: 67%

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The BAG-1 cochaperone is a negative regulator of p73-dependent transcription

O’Connor

Brimmell

et al. 2009

Br J Cancer

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High-level expression of Bcl-2 associated athanogene (BAG-1) protects cancer cells from stress-induced cell death and growth inhibition. These protective effects of BAG-1 are dependent on interactions with the HSC70 and HSP70 chaperones. However, the key stress-response molecules that are regulated by a BAG-1/chaperone mechanism have not been identified. In this study, we investigated the effects of BAG-1 overexpression on the function of p53 family proteins, p53, p63 and p73. Overexpression of BAG-1 isoforms interfered with the transactivating activity of p73 and p63, but had modest and variable effects on p53-dependent transcription. p73 and BAG-1 interacted in intact cells and overexpression of BAG-1 decreased the expression of p73. siRNAmediated ablation of endogenous BAG-1 increased the activity of a p73-responsive promoter and this was reversed by knock-down of p73. The ability of BAG-1 to modulate p73 activity and expression, and to interact with p73 were dependent on amino acid residues required for the interaction of BAG-1 with HSC70 and HSP70. These results show that BAG-1 inhibits the transactivating functions of p73 and provide new insight into the mechanisms that control the expression of p73. Inhibition of p73 function may be one mechanism that contributes to the pro-survival activity of BAG-1.

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Section: Inhibition Of P73a Function By Bag-1s Requires Helix 2 and 3supporting

confidence: 84%

Section: Bag-1s (G3e2)supporting

confidence: 67%

The BAG-1 cochaperone is a negative regulator of p73-dependent transcription

O’Connor

Brimmell

et al. 2009

Br J Cancer

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“…Optimized expression constructs for human Bag1-S (hBag1-S), Bag1-L (hBag1-L), and Bag1-S fused to a heterologous nuclear localization signal (NLS) (NLS-hBag1-S), nuclear export signal (NES) (NES-hBag1-S), hBag1-L with point mutations in the BAG domain, or hBag1-S fused to glutathione S-transferase (GST) (GST-hBag1-S) have been previously described (12,30,48).…”

Section: Methodsmentioning

confidence: 99%

“…(hBag1-L-H2) results in a greatly reduced ability to interact with heat shock proteins (30) (Fig. 3C) while Bag1-L E226A,K230A…”

Section: Bag1-l Interacts With C-junmentioning

confidence: 99%

“…Since bag1 mRNA knockdown would result in depletion of both the Bag1-S and Bag1-L proteins, which have different and VOL. 30,2010 STIMULATION OF c-Jun ACTIVITY BY Bag1-L 3847 sometimes opposing functions in cell death, we decided to investigate the consequences of Bag1-L overexpression. Ectopic Bag1-L expression exacerbated neuronal cell death induced by potassium deprivation, whereas Bag1-L⌬BD had no significant effect compared to results for the control (Fig.…”

Section: N-terminal Phosphorylation Is Required For C-jun Interactionmentioning

confidence: 99%

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