The SLTM [SAF (scaffold attachment factor)-like transcription modulator] protein contains a SAF-box DNA-binding motif and an RNA-binding domain, and shares an overall identity of 34% with SAFB1 {scaffold attachment factor-B1; also known as SAF-B (scaffold attachment factor B), HET [heat-shock protein 27 ERE (oestrogen response element) and TATA-box-binding protein] or HAP (heterogeneous nuclear ribonucleoprotein A1-interacting protein)}. Here, we show that SLTM is localized to the cell nucleus, but excluded from nucleoli, and to a large extent it co-localizes with SAFB1. In the nucleus, SLTM has a punctate distribution and it does not co-localize with SR (serine/arginine) proteins. Overexpression of SAFB1 has been shown to exert a number of inhibitory effects, including suppression of oestrogen signalling. Although SLTM also suppressed the ability of oestrogen to activate a reporter gene in MCF-7 breast-cancer cells, inhibition of a constitutively active β-galactosidase gene suggested that this was primarily the consequence of a generalized inhibitory effect on transcription. Measurement of RNA synthesis, which showed a particularly marked inhibition of [3H]uridine incorporation into mRNA, supported this conclusion. In addition, analysis of cell-cycle parameters, chromatin condensation and cytochrome c release showed that SLTM induced apoptosis in a range of cultured cell lines. Thus the inhibitory effects of SLTM on gene expression appear to result from generalized down-regulation of mRNA synthesis and initiation of apoptosis consequent upon overexpressing the protein. While indicating a crucial role for SLTM in cellular function, these results also emphasize the need for caution when interpreting phenotypic changes associated with manipulation of protein expression levels.
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November 2007
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Research Article|
October 12 2007
A novel member of the SAF (scaffold attachment factor)-box protein family inhibits gene expression and induces apoptosis
Ching Wan Chan;
Ching Wan Chan
1
*Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, U.K.
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Youn-Bok Lee;
Youn-Bok Lee
1
*Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, U.K.
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James Uney;
James Uney
*Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, U.K.
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Andrea Flynn;
Andrea Flynn
*Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, U.K.
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Jonathan H. Tobias;
Jonathan H. Tobias
†Rheumatology Unit, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, U.K.
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Michael Norman
Michael Norman
2
*Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, U.K.
2To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 01 2007
Revision Received:
June 25 2007
Accepted:
July 13 2007
Accepted Manuscript online:
July 13 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 407 (3): 355–362.
Article history
Received:
February 01 2007
Revision Received:
June 25 2007
Accepted:
July 13 2007
Accepted Manuscript online:
July 13 2007
Citation
Ching Wan Chan, Youn-Bok Lee, James Uney, Andrea Flynn, Jonathan H. Tobias, Michael Norman; A novel member of the SAF (scaffold attachment factor)-box protein family inhibits gene expression and induces apoptosis. Biochem J 1 November 2007; 407 (3): 355–362. doi: https://doi.org/10.1042/BJ20070170
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