cDNA cloning of a novel rainbow trout SRY-type HMG box protein, rtSox23, and its functional analysis

Yamashita, Atsushi; Suzuki, Shin; Fujitani, Kazuko; Kojima, Miho; Kanda, Hiromi; Ito, Michihiko; Takamatsu, Nobuhiko; Yamashita, Shinya; Shiba, Tadayoshi

doi:10.1016/s0378-1119(98)00047-x

Cited by 21 publications

(23 citation statements)

References 37 publications

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“…1C) , indicating that the ICA12 cDNA is the human homologue of Sox13 from mouse. However, our identification of a 604 amino acid open reading frame for ICA12, called SOX13 herea f t e r, is in conflict with a recent report by Roose et al SOX13 shares high amino acid similarity to Sox23 from rainbow trout (32) and to Sox12 from Xenopus (33) (Fig. 1C) , which are more similar to SOX13 than to any other SOX protein.…”

Section: R E S U Lt Scontrasting

confidence: 94%

“…SOX13 contains an unusual leucine zipper motif of the form LX 5 Q L X 5 Q L X 5 Q L , which may mediate specific protein-protein interactions during nuclear import and transcriptional regulation through heterodimerization. In rainbow trout Sox23, the leucine zipper interacts with nucleoporin p62, which in turn interacts with the nuclear pore complex (32). We have demonstrated that SOX13 can form homodimers through the leucine zipper/glutamine-rich region and that homodimerization significantly reduces DNA binding.…”

Section: Discussionmentioning

confidence: 88%

“…Furthermore, the nuclear localization signal shared by SOX protein HMG domains (51) may also be obscured in the SOX13 homodimer. Exposure of the nuclear localization signal to importins may be facilitated through heterodimerization with factors such as p62 nucleoporin, which is known to interact with rtSox23 (32).…”

Section: Discussionmentioning

confidence: 99%

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Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets.

et al. 2000

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The SOX (sex-determining region [SRY]-type high mobility group [HMG] box) family of transcription factors play key roles in determining cell fate during organ development. In this study, we have identified a new human SOX gene, S O X 1 3, as encoding the type 1 diabetes autoantigen, islet cell antigen 12 (ICA12). Sequence analysis showed that SOX13 belongs to the class D subgroup of SOX transcription factors, which contain a leucine zipper motif and a region rich in glutamine. SOX13 autoantibodies occurred at a significantly higher frequency among 188 people with type 1 diabetes (18%) than among 88 with type 2 diabetes (6%) or 175 healthy control subjects (4%). Deletion mapping of the antibody epitopes showed that the autoantibodies were primarily directed against an epitope requiring the majority of the protein. S O X 1 3 R N A was detected in most human tissues, with the highest levels in the pancreas, placenta, and kidney. Immunohistochemistry on sections of human pancreas identified SOX13 in the islets of Langerhans, where staining was mostly cytoplasmic. In mouse pancreas, Sox13 was present in the nucleus and cytoplasm of -cells as well as other islet cell types. Recombinant SOX13 protein bound to the SOX consensus DNA motif AACAAT, and binding was inhibited by homodimer formation. These observations-along with the known molecular interactions of the closely related protein, rainbow trout Sox23-suggest that SOX13 may be activated for nuclear import and DNA binding through heterodimer formation. In conclusion, we have identified ICA12 as the putative transcription factor SOX13 and demonstrated an increased frequency of autoantibody reactivity in sera from type 1 diabetic subjects compared with type 2 diabetic and healthy control subjects. T ype 1 diabetes results from the destruction of pancreatic islet -cells by an autoimmune response to -cell constituents, which is initiated by an unknown environmental agent acting on a susceptible genetic background. Identification of GAD (1), a family of tyrosine phosphatase-like proteins variously designated islet cell antigen 512 (ICA512)/IA-2/IA-2 (2,3), and insulin (4) as autoantigens in type 1 diabetes has led to the proposal of several mechanisms for the initiation and progression of islet autoimmunity. These include molecular mimicry between GAD and coxsackievirus B (5) or between ICA512 and rotavirus (6), hyperexpression of GAD in response to metabolic stress (7), and lack of tolerance to (pro)insulin as a consequence of genetic variation of proinsulin expression levels in the thymus (8,9). The multifactorial nature of type 1 diabetes and the association of numerous environmental agents with the disease (10) suggest that there may be multiple pathways leading to -cell autoimm u n i t y. To attain a better understanding of the pathogenesis of type 1 diabetes, the autoimmune response to islet -c e l l s needs to be fully characterized.In a search for novel diabetes-associated autoantigens, the screen of an islet cDNA expression library with type 1 diabetes sera tha...

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Section: R E S U Lt Scontrasting

confidence: 94%

Section: Discussionmentioning

confidence: 88%

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Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets.

et al. 2000

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“…This pattern is present in many gene regulatory proteins (Yamashita et al, 1998). Leucine zipper motifs have also been found in rat Nup107p and yeast Nup120p Aitchison et al, 1995a).…”

Section: Figmentioning

confidence: 76%

Localization of a Human Nucleoporin 155 Gene (NUP155) to the 5p13 Region and Cloning of Its cDNA

et al. 1999

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“…2c). Like mSox-13, hSOX-13 contained an N-terminal leucine zipper-Q region (aa 127-203), as is also found in mSox-6, rtSox-6/SOX-LZ, and rtSox-23 (3,20,24) (Fig. 2c).…”

mentioning

confidence: 71%

TheSox-13Gene: Structure, Promoter Characterization, and Chromosomal Localization

Roose¹,

Korver²,

Boer³

et al. 1999

Genomics

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cDNA cloning of a novel rainbow trout SRY-type HMG box protein, rtSox23, and its functional analysis

Cited by 21 publications

References 37 publications

Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets.

Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets.

Localization of a Human Nucleoporin 155 Gene (NUP155) to the 5p13 Region and Cloning of Its cDNA

TheSox-13Gene: Structure, Promoter Characterization, and Chromosomal Localization

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