Disease relevance of STRA13

• Hypoxia treatment of mammalian cells transiently expressing STRA13 protein showed that stability of pSTRA13 is not affected by hypoxia or VHL [1].
• Introduction of wild type VHL transgene into clear cell renal carcinoma restored low level expression of STRA13 [1].
• DEC1 (STRA13) protein expression relates to hypoxia- inducible factor 1-alpha and carbonic anhydrase-9 overexpression in non-small cell lung cancer [2].
• Epidermal growth factor receptor is down-regulated by a 10,400 MW protein encoded by the E3 region of adenovirus [3].
• The E3/19K protein of human adenovirus type 2 binds to HLA class I antigens and blocks their terminal glycosylation and cell surface expression [4].

Psychiatry related information on STRA13

• We have investigated immunohistochemically the expression of exon 3-derived fragment (E-3) of tau protein in brains of patients with Alzheimer's disease (AD) and other neurodegenerative diseases in which the abnormal accumulation of tau protein takes place [5].

High impact information on STRA13

• Using a series of virus deletion mutants, the gene responsible for EGF-R down-regulation was mapped to the E3 transcription unit [3].
• E3 ubiquitin ligases as T cell anergy factors [6].
• We also observe that the phosphorylation of the endogenous HLA molecules is grossly impaired in a human cell line transfected with the Ad2 EcoRI D fragment containing the E3/19k gene [7].
• We conclude that the E3/19k protein inhibits the phosphorylation of the MHC heavy chains and that this may be one of the important functions of this protein in infected cells [7].
• One of these proteins, called E3/19k, binds to newly synthesized MHC molecules in the rough endoplasmic reticulum (RER) and inhibits their trafficking to the cell surface [7].

Chemical compound and disease context of STRA13

• Mutation of the parkin gene, which encodes an E3 ubiquitin-protein ligase, is the major cause of autosomal recessive juvenile parkinsonism (ARJP) [8].
• The adenovirus E3 region-encoded 14.7K protein inhibits tumor necrosis factor alpha (TNF-alpha)-induced apoptosis and arachidonic acid synthesis [9].
• We have reported that an 11,600-Da nuclear membrane glycoprotein named adenovirus death protein (ADP), encoded by the E3 region, is required for the efficient death (lysis) of adenovirus (Ad)-infected cells [10].

Biological context of STRA13

• Forced expression of STRA13 induced apoptosis, in agreement with the STRA13 activation effect on the Fas promoter [11].
• STRA13 is a pVHL-dependent bHLH transcription factor up-regulated on the mRNA level in multiple cancer cell lines and implicated recently in the regulation of immune cell homeostasis and autoimmunity [11].
• Thus, we characterize a novel STRA13-associated transcription repression complex and provide a link between cell cycle regulation and STRA13 activity [12].
• Assignment1 of the human Stra13 gene (STRA13) to chromosome 3p26 by in situ hybridization [13].
• DEC1/STRA13/SHARP2 is a transcription factor of the bHLH family that has been suggested to play key roles in mammalian cell differentiation, the cell cycle and circadian regulation [14].

Anatomical context of STRA13

• RESULTS: STRA13 was commonly expressed in epithelial cells of normal and neoplastic tissues where it was confined mostly to the nucleus [15].
• E3 transcripts are present in the myeloid, B-lymphoid, and erythroid lineages, absent in nonhematopoietic cells, and encode a highly hydrophobic, potentially phosphorylated polypeptide of unknown function with significant homology to a putative protein expressed in myeloid cells [16].
• E3/19K resides in the endoplasmic reticulum where it binds to MHC class I molecules, thereby preventing their transport to the cell surface [17].
• We reported previously that certain murine fibroblasts infected with group C human adenoviruses become sensitive to cytolysis by TNF, and that a 14,700 m.w. (14.7K) protein encoded by the E3 transcription unit protects the cells from TNF cytolysis [18].
• The E3 transmembrane proteins 10.4 and 14.5 form a complex that down-regulates the epidermal growth factor receptor and apoptosis receptors from the cell surface by diverting them to endosomes/lysosomes for degradation [19].

Associations of STRA13 with chemical compounds

• These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination [20].
• The E3/16 protein is the precursor to the E3/19 glycoprotein and is around 1500 daltons larger than the unglycosylated E3/19O protein [21].
• By generating stable E3 transfectants expressing 10.4-14.5 proteins with alanine substitutions in these motifs, we show that 3 of the 5 motifs are essential for functional activity [19].
• It acts as an E3 ubiquitin-protein ligase as well as a steroid hormone receptor coactivator [22].
• Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact [23].

Other interactions of STRA13

• The von Hippel-Lindau (VHL) tumour suppressor gene encodes a substrate-specifying component of an E3 ubiquitin ligase that targets hypoxia-inducible factor (HIF) alpha subunits for degradation under normoxia [24].
• Investigation of the molecular mechanisms of STRA13 nucleo-cytoplasmic shuttling suggested that STRA13 employs nuclear import/export that utilises the NLS/NES motifs situated within the N-terminus and in the middle of the protein [15].
• These results indicate that E3 is a hematopoietic-specific gene that is an immediate target for the activated RAR alpha during myelopoiesis [16].

Analytical, diagnostic and therapeutic context of STRA13

• HECT domain E3 ligases not only recognize, but also directly catalyze, ligation of ubiquitin to their protein substrates [25].
• Crystallization and preliminary X-ray diffraction studies of colicin E3 immunity protein [26].
• More recently, however, the reintroduction of the E3 region into oncolytic adenoviruses has been found to positively influence antitumor efficacy in preclinical models and clinical trials [27].
• Like HAV E3, a majority of the BAV-1 E3 region was not essential for growth in cell culture, as demonstrated by the construction of a recombinant BAV-1 lacking 60% of the putative E3 region [28].
• The E-3 regions of PAV types 1, 2 and 3 were further characterized by Northern blot analysis and 5' and 3' end mapping of the transcripts by S1 nuclease analysis [29].

References