Disease relevance of NCKIPSD

• Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins [1].
• Heat-regulated expression of the hepatitis B virus surface antigen in the human Wish cell line [2].
• The mtHSV replicated in and lysed U251 (human glioma cells), EJ (human bladder cells), and S-180 (mice sarcoma cells), but not Wish (human amnion cells) cells [3].
• We studied the sensitivity of several human cancer cell strains (HeLa, HT1080, SPC-A1, and ACHN) and normal cell strains (MRC-5 and Wish) to mumps virus (MuV) S79, a live attenuated vaccine strain [4].
• The balhimycin biosynthetic gene cluster of the glycopeptide producer Amycolatopsis balhimycina includes a gene (orf1) with unknown function. orf1 shows high similarity to the mbtH gene from Mycobacterium tuberculosis [5].

High impact information on NCKIPSD

• SPIN90/WISH (SH3 protein interacting with Nck, 90 kDa/Wiskott-Aldrich syndrome protein (WASP) interacting SH3 protein) regulates actin polymerization through its interaction with various actin-regulating proteins [6].
• Finally, in response to chemically induced long-term potentiation, SPIN90/WISH associated with PSD-95 and was redistributed to dendritic spines [6].
• Our results suggest that SPIN90/WISH associates with PSD-95, and so becomes localized to dendritic spines where it modulates actin dynamics to control dendritic spinogenesis [6].
• The resulting chimeric protein consists of AT-hooks, methyltransferase, and transcription repressor domains of MLL in addition to the AF3p21 proline-rich domain and NLS but not the AF3p21 SH3 domain [7].
• Screening of a genomic DNA library, prepared from leukemic cell DNA, identified rearranged clones composed of MLL and a novel gene on chromosome 3p21 (AF3p21) [7].

Biological context of NCKIPSD

• The AF3p21 gene encodes a protein of 722 amino acids, which contains an Src homology 3 (SH3) domain, a proline-rich domain, and a bipartite nuclear localizing signal (NLS) [7].
• SPIN90 was phosphorylated by ERK1, which was, itself, activated by cell adhesion and platelet-derived growth factor [8].
• Such phosphorylation of SPIN90 likely promotes the interaction of the SPIN90.betaPIX.WASP complex and Nck [8].
• Taken these findings suggest that SPIN90 participates in reorganization of the actin cytoskeleton and in actin-based cell motility [9].
• These results suggest the possibility that AF3p21 protein plays a role in signal transduction in the nucleus [10].

Anatomical context of NCKIPSD

• SPIN90 (SH3 protein interacting with Nck, 90 kDa), an adaptor protein that is developmentally regulated during cardiac myocyte differentiation [11].
• SPIN90 is able to bind to the first and third SH3 domains of Nck, in vitro, and is colocalized with Nck at sarcomere Z-discs within cardiac myocytes [11].
• Here, we provide evidence for the involvement of SPIN90 in the regulation of actin cytoskeleton and actin comet tail formation [9].
• SPIN90 was broadly expressed in human tissues; in particular, it was highly expressed in heart, brain, and skeletal muscle, and its expression was developmentally regulated during cardiac myocyte differentiation [11].
• The SPIN90.betaPIX.WASP complex was stable, even in suspended cells, suggesting SPIN90 serves as an adaptor molecule to recruit other proteins to Nck at focal adhesions [8].

Associations of NCKIPSD with chemical compounds

• SPIN90 is a widely expressed Nck-binding protein that contains one Src homology 3 (SH3) domain, three Pro-rich motifs, and a serine/threonine-rich region, and is known to participate in sarcomere assembly during cardiac myocyte differentiation [8].
• And when coexpressed with phosphatidylinositol 4-phosphate 5 kinase, SPIN90 was observed within actin comet tails [9].
• This study demonstrated that 1 microM U-75412E was unable to modify these parameters, while higher concentrations (6-75 microM) had a cytotoxic effect on Wish cells [12].
• In all glycopeptide biosynthetic gene clusters the orf1-like gene is always located downstream of the gene encoding the last module of the NRPS [5].
• In the present study we used Namalwa, Wish and C6 cell lines in order to investigate the correlation between gene reorganisations and their expression [13].

Physical interactions of NCKIPSD

• SPIN90/WISH interacts with PSD-95 and regulates dendritic spinogenesis via an N-WASP-independent mechanism [6].
• It appears that betaPIX, WASP, and SPIN90 form a complex that interacts with Nck in a manner dependent upon cell adhesion to extracellular matrix [8].

Other interactions of NCKIPSD

• We used in vitro binding assays and yeast two-hybrid screening analysis to identify Nck, betaPIX, Wiscott-Aldrich syndrome protein (WASP), and ERK1 as SPIN90-binding proteins [8].
• Interaction of SPIN90 with the Arp2/3 complex mediates lamellipodia and actin comet tail formation [9].
• Genomic organization, tissue expression, and cellular localization of AF3p21, a fusion partner of MLL in therapy-related leukemia [10].
• In addition, we found that overexpression of the SPIN90 SH3 domain or Pro-rich region, respectively, abolished SPIN90.Nck and SPIN90.betaPIX interactions, resulting in detachment of cells from extracellular matrix [8].
• The AF3p21 gene encodes a nuclear protein with a molecular mass of 80 kDa, and this protein has SH3 and proline-rich domains [14].

Analytical, diagnostic and therapeutic context of NCKIPSD

• Western blot and immunocytochemical analyses showed that AF3p21 protein has an apparent molecular weight of 80 kDa and is localized exclusively in the cell nucleus [10].
• The CA 125 present in various biological fluids (serum, cyst, peritoneal and amniotic fluids, human milk, seminal plasma, cervical mucus and Wish culture medium), was characterized by gel chromatography and immunoblotting analysis [15].
• Wish to live vs. Wish to die: a cross sectional study of suicidal inpatients [16].
• At the concentration of 50-100 micrograms LX/ml cell culture medium, LX completely blocked the growth of the cells of several transformed cell lines (HeLa, Hep-2, MG-63, Chang liver, Wish, FL-Amnion) as well as the normal (Flow 2000 and Flow 13000) [17].

References