Disease relevance of ST13

• Characterization of FAM10A4, a member of the ST13 tumor suppressor gene family that maps to the 13q14.3 region associated with B-Cell leukemia, multiple myeloma, and prostate cancer [1].
• Expression of ST13 in colorectal cancer and adjacent normal tissues [2].
• ST13 is mostly expressed in colorectal epithelia and adenocarcinoma cells [2].
• But there were no significant differences in the expression of ST13 as compared with different Dukes' stage, tumor differentiation grade, invasion depth, lymph node metastasis and disease-specific survival [3].
• These include the co-chaperone ST13, which stabilizes heat-shock protein 70, a modifier of alpha-synuclein misfolding and toxicity [4].

High impact information on ST13

• This mutational analysis indicates that Hip's TPR is required for binding of Hip with hsp70's ATPase domain [5].
• Truncations from Hip's N terminus resulted in an apparent loss of Hip homo-oligomerization, but these mutants retained association with hsp70 and were recovered in receptor complexes [5].
• P48 may play an important role in growth and development of normal and abnormal (leukemic) hematopoietic and nonhematopoietic cells [6].
• A 48-kDa glycoprotein (P48) which mediates this differentiation factor activity has been purified to homogeneity from Reh cell conditioned medium, and a polyclonal neutralizing antiserum has been produced [6].
• Here we show that Fbx2, a brain-enriched F-box protein implicated in the ubiquitination of glycoproteins discarded from the endoplasmic reticulum, binds the co-chaperone/ubiquitin ligase CHIP (C terminus of Hsc-70-interacting protein) through a unique N-terminal PEST domain in Fbx2 [7].

Biological context of ST13

• This gene has been shown to be part of a now six-member family of genes with high homology to the ST13 tumor suppressor gene [1].
• Evaluation of ST13 gene expression in colorectal cancer patients [3].
• We identified a novel gene ST13 from a subtractive cDNA library of normal intestinal mucosa in 1993, more studies showed that ST13 was a co-chaperone of Hsp70s [3].
• Introducing human Hip into yeast enhances hormone-dependent activation of a reporter gene by glucocorticoid receptor (GR) [8].
• CHIP (C terminus of Hsc-70 interacting protein) is an E3 ligase that links the protein folding machinery with the ubiquitin-proteasome system and has been implicated in disorders characterized by protein misfolding and aggregation [9].

Anatomical context of ST13

• The expression levels of the ST13 gene were significantly decreased in primary tumors compared with adjacent mucosa (P<0.05) [3].
• P48 is a cytokine recently identified in the supernatant of the human null cell leukemia cell line Reh, which induces differentiation and cytolytic activity in HL-60 cells [10].
• In the present study we examined the ability of P48 to stimulate cytokine release by human peripheral blood monocytes [10].
• Overexpressing Hip enhances the refolding of the heat-inactivated reporter enzyme luciferase expressed in hamster lung fibroblasts [11].
• Acinar-like activity of the enhancer can be reconstituted in HeLa cells by the introduction of P48, HEB, and the PDX1-containing trimeric homeodomain complex that binds the second pancreatic element of the enhancer [12].

Associations of ST13 with chemical compounds

• Differential display reverse transcription-PCR revealed that fraxin upregulated antiapoptotic genes (clusterin and apoptosis inhibitor 5) and tumor suppressor gene (ST13) [13].
• COS or HEK-293 cells expressing OK-GC receptor protein were activated by uroguanylin, guanylin, or ST13 peptides [14].
• Because Hip does not similarly enhance signaling by mineralocorticoid, progesterone, or estrogen receptors, a general effect on transcription can be excluded [8].
• Because the budding yeast Saccharomyces cerevisiae contains orthologs for most of the receptor-associated chaperones yet lacks an orthologous Hip gene, we exploited the well-established yeast model for steroid receptor function to ask whether Hip can alter steroid receptor function in vivo [8].
• The cytokine-inducing activity of P48 was extremely sensitive to heat treatment but could not be eliminated by using polymyxin B [10].

Other interactions of ST13

• Binding of Hip to hsp70's ATPase domain was lost with deletions from the TPR and from an adjoining highly charged region; correspondingly, these Hip mutant forms were not recovered in receptor complexes [5].
• The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13 [15].
• CHIP (carboxyl terminus of Hsc70-interacting protein) promotes basal and geldanamycin-induced degradation of estrogen receptor-alpha [16].
• CHIP (carboxyl terminus of Hsc70-interacting protein) is such a cofactor that interacts with Hsc70 and, in general, attenuates its most well characterized functions [17].
• During proteasomal sorting BAG-1 can cooperate with another co-chaperone, the carboxyl terminus of Hsc70-interacting protein CHIP [18].

Analytical, diagnostic and therapeutic context of ST13

• The P56-P48 interaction was confirmed in human cells by co-immunoprecipitation assays and confocal microscopy [19].
• Gel filtration assays revealed that P56 binds to the large eIF-3 complex that contains P48 [19].
• Western blot analysis revealed that P48 partitioned exclusively into the detergent phase, suggesting an integral membrane association [20].
• In further studies designed to examine the biosynthesis and function of P48, surface immunofluorescence flow cytometry analysis as well as 125I surface labeling and immunoprecipitation, revealed the presence of P48 on the surface of Reh cells [20].
• Subsequent studies using PCR and Southern analysis revealed P48 sequences in DNA isolated from Mycoplasma fermentans but not M. hominis, M.iowae, M.synoviae or M.lypophilum [21].

References