SAFB2, a new scaffold attachment factor homolog and estrogen receptor corepressor.
We have characterized previously the nuclear matrix protein/scaffold attachment factor (SAFB) as an estrogen receptor corepressor and as a potential tumor suppressor gene in breast cancer. A search of the human genome for other potential SAFB family members revealed that KIAA00138 (now designated as SAFB2) has high homology to SAFB (now designated as SAFB1). SAFB1 and SAFB2 are mapped adjacent to each other on chromosome 19p13.3 and are arranged in a bidirectional divergent configuration (head to head), being separated by a short (<500 bp) GC-rich intergenic region that can function as a bidirectional promoter. SAFB1 and SAFB2 share common functions but also have unique properties. As shown previously for SAFB1, SAFB2 functions as an estrogen receptor corepressor, and its overexpression results in inhibition of proliferation. SAFB1 and SAFB2 interact directly through a C-terminal domain, resulting in additive repression activity. They are coexpressed in a number of tissues, but unlike SAFB1, which is exclusively nuclear, SAFB2 is found in the cytoplasm as well as the nucleus. Consistent with its cytoplasmic localization, we detected an interaction between SAFB2 and vinexin, a protein involved in linking signaling to the cytoskeleton. Our findings suggest that evolutionary duplication of the SAFB gene has allowed it to retain crucial functions, but also to gain novel functions in the cytoplasm and/or nucleus.
Townson
Steven M
SM
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Dobrzycka
Klaudia M
KM
Lee
Adrian V
AV
Air
Mamie
M
Deng
Wanleng
W
Kang
Kaiyan
K
Jiang
Shiming
S
Kioka
Noriyuki
N
Michaelis
Kai
K
Oesterreich
Steffi
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D017931:DNA Primers; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D036961:Matrix Attachment Region Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; D011960:Receptors, Estrogen; D012097:Repressor Proteins; C109132:SAFB protein, human; C486369:SAFB2 protein, human