Lee, San San, Crabb, Simon J., Janghra, Nari, Carlber, Carsten, Williams, Ann C., Cutress, Ramsey I., Packham, Graham and Hague, Graham
Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis
Experimental Cell Research, 313, (15), . (doi:10.1016/j.yexcr.2007.06.010).
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In oral cancers, cytoplasmic BAG-1 overexpression is a marker of poor prognosis. BAG-1 regulates cellular growth, differentiation and survival through interactions with diverse proteins, including the vitamin D receptor (VDR), a key regulator of keratinocyte growth and differentiation. BAG-1 is expressed ubiquitously in human cells as three major isoforms of 50 kDa (BAG-1L), 46 kDa (BAG-1M) and 36 kDa (BAG-1S) from a single mRNA. In oral keratinocytes BAG-1L, but not BAG-1M and BAG-IS, enhanced VDR transactivation in response to 1 alpha,2S-dihydroxyvitamin D-3. BAG-1L was nucleoplasmic and nucleolar, whereas BAG-1S and BAG-1M were cytoplasmic and nucleoplasmic in localisation. Having identified the nucleolar localisation sequence in BAG-1L, we showed that mutation of this sequence did not prevent BAG-1L from potentiating VDR activity. BAG-1L also potentiated transactivation of known vitamin-D-responsive gene promoters, osteocalcin and 24-hydroxylase, and enhanced VDR-dependent transcription and protein expression of the keratinocyte differentiation marker, involucrin. These results demonstrate endogenous gene regulation by BAG-1L by potentiating nuclear hormone receptor function and suggest a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1 alpha,25-dihydroxyvitamin D-3. By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis.
|Digital Object Identifier (DOI):
||promoter, protein, dna-binding, transcriptional activity, 24-hydroxylase, 1, cancer, transcription, nucleolar localisation sequence, in-vitro, oral keratinocytes, 25-dihydroxyvitamin d-3
|10 September 2007||Published|
||11 Sep 2008
||16 Apr 2017 17:28
|Further Information:||Google Scholar|
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