Disease relevance of SNW1

• Chromatin immunoprecipitation studies revealed that endogenous NCoA62/SKIP associated in a 1,25-dihydroxyvitamin D3-dependent manner with VDR target genes in ROS17/2.8 osteosarcoma cells [1].
• The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity [2].
• RESULTS: Skip metastases (negative central and positive lateral or mediastinal compartments) were found in 13 (19.7%) of 66 papillary, 0 of 8 follicular, and 30 (21.3%) of 141 medullary thyroid cancers [3].
• BACKGROUND: Skip metastasis to mediastinal lymph nodes is a well-known phenomenon in non-small cell lung cancer (NSCLC) [4].
• Re-evaluation of Axillary Skip Metastases in the Era of Sentinel Lymph Node Biopsy in Breast Cancer [5].

High impact information on SNW1

• Furthermore, Ski-interacting protein (SKIP) was isolated as a binding protein for PABP2 using the yeast two-hybrid system [6].
• We identified SKIP (Ski-interacting protein) as a CBF1 binding protein in a yeast two-hybrid screen [7].
• We showed that FAM53B bound 14-3-3 chaperones, as well as SKIIP proteins, adaptor proteins connecting DNA-binding proteins to modulators of transcription. smp inactivation with morpholinos led to delayed epiboly and reduced embryonic size [8].
• The mechanism through which NCoA62/SKIP functions in VDR-activated transcription is unknown [1].
• Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing [1].

Biological context of SNW1

• Coexpression of NCoA-62 in a vitamin D-responsive transient gene expression system augmented 1, 25-dihydroxyvitamin D3-activated transcription, but it had little or no effect on basal transcription or gal4-VP16-activated transcription [9].
• This suggests that NCoA62/SKIP functions at a distal step in the transactivation process [10].
• Using a series of reporter plasmids, we show that Skip is a potent transcriptional activator of many different promoters, the activity of which was also mapped to the conserved core SNW domain of the protein [11].
• Furthermore, the combination of Skip and Ski can successfully overcome the G1 arrest and flat cell phenotype induced by pRb [12].
• We further found that Prp45 activated the transcription of a reporter gene in S. cerevisiae when targeted to DNA [13].

Anatomical context of SNW1

• Taken together, these data show that NCoA62/SKIP has properties that are consistent with those of nuclear receptor coactivators and with RNA spliceosome components, thus suggesting a potential role for NCoA62/SKIP in coupling VDR-mediated transcription to RNA splicing [1].
• To explore potential mechanisms, NCoA62/SKIP-interacting proteins were purified from HeLa cell nuclear extracts and identified by mass spectrometry [1].
• In the present study, we identified a nuclear localization sequence in the COOH terminus of NCoA62/SKIP and showed that NCoA62/SKIP was targeted to nuclear matrix subdomains [1].
• SNW1/SKIP is involved in the regulation of transcription and mRNA splicing, whereas stathmin is involved in stabilization of microtubules [14].
• Like Ski, Skip is expressed in multiple tissue types and is localized to the cell nucleus [15].

Associations of SNW1 with chemical compounds

• Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription [16].
• NCoA-62 also interacted with retinoid receptors, and its expression enhanced retinoic acid-, estrogen-, and glucocorticoid-mediated gene expression [9].
• We identified in Dictyostelium a gene snwA containing a region of similarity to SH2 domains of higher eukaryotes. snwA is homologous to a novel human gene SNW1 and to Bx42 from Drosophila melanogaster, a gene coding for a chromatin binding protein responsive to 20-OH-ecdysone. snwA has one mRNA transcript of an approximate size of 2.5 kb [17].

Physical interactions of SNW1

• Using a cytoplasmic two-hybrid screening approach, we find that this portion of CHES1 interacts with Ski-interacting protein (SKIP; NCoA-62), which is a transcriptional co-regulator known to associate with repressor complexes [18].
• The liganded VDR also formed a ternary complex with NCoA-62/SKIP and SRC proteins in vitro [16].
• Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription [19].
• It showed that human LNX interacted with Ski interacting protein (SKIP) via PDZ domains [20].
• Screening by the yeast two-hybrid system revealed that the MIBP1 protein interacts with the Ski-interacting protein (SKIP) [21].

Regulatory relationships of SNW1

• Therefore, elevated expression of PPIL1 may play an important role in proliferation of cancer cells through the control of SNW1/SKIP and/or stathmin [14].
• The purpose of this paper is to briefly review salient features of the coactivators involved in VDR-activated transcription and to focus on our current understanding of NCoA-62 and its interplay with other nuclear receptor coactivator proteins [22].

Other interactions of SNW1

• Competition experiments using LXXLL peptides showed that NCoA-62/SKIP and SRC coactivators contact different domains of the VDR-RXR heterodimer [16].
• Occult fallopian tube cancer diagnosed at prophylactic surgery in BRCA mutation carriers was exclusively distal. "Skip" areas of high-grade dysplasia were only seen in 2 patients, both of whom were BRCA mutation carriers [23].

Analytical, diagnostic and therapeutic context of SNW1

• CONCLUSIONS: Skip metastasis are frequent in non-small-cell lung cancer and complete dissection of hilar and mediastinal lymph nodes should remain the surgical standard procedure for this disease [24].
• CONCLUSIONS: Skip laminectomy was less invasive to the posterior extensor mechanism including the deep extensor muscles than open-door laminoplasty [25].

References