Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desmoyokin was identified as a desmosomal plaque protein. We previously demonstrated that desmoyokin is identical to a protein encoded by a human gene, AHNAK, whose expression is suppressed in neuroblastoma cells. Although this protein is distributed in the cytoplasm and the nucleus in various cells, it is associated closely with the plasma membrane in keratinocytes. In keratinocytes, desmoplakin translocates from the cytoplasm to the plasma membrane following both high calcium switch and protein kinase C (PKC) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the low calcium medium, the desmoyokin/AHNAK protein resides diffusely in the cytoplasm and the nucleus. However, 2 h after shift to the high calcium medium, the desmoyokin/AHNAK protein localized to the cell boundary in all cells in a pattern similar to that of desmoplakin. Selective PKC inhibitors completely inhibited the calcium-induced translocation of the desmoyokin/AHNAK protein, but the inhibition of desmoplakin translocation by these inhibitors was only partial. TPA also induced translocation of both the desmoyokin/AHNAK protein and desmoplakin, which was completely inhibited by PKC inhibitors. The calcium-induced phosphorylation of the desmoyokin/AHNAK protein was confirmed by immunoprecipitation using [32P]orthophosphate-labeled keratinocytes. Furthermore, the study of extractability with non-ionic detergent indicated that desmoplakin, but not the desmoyokin/AHNAK protein, is associated with the cytoskeleton. These results suggested an involvement of PKC in the translocation of the desmoyokin/AHNAK protein in keratinocytes. It was, however, also suggested that different mechanisms are likely involved in the translocation of the desmoyokin/AHNAK protein and desmoplakin.
 ...
PMID:Regulation of translocation of the desmoyokin/AHNAK protein to the plasma membrane in keratinocytes by protein kinase C. 769 24

AHNAK is a newly identified human gene notable for the exceptional size (c.a. 700 kD) and structure of its product, and for the repression of its expression in human neuroblastoma cells. Here we report the identification and partial characterization of the protein encoded by AHNAK. The protein is located principally (but not exclusively) in the nucleus and is phosphorylated on both serine and threonine. The abundance of the protein increases appreciably when cells withdraw from the division cycle, in response to either withdrawal of serum (fibroblasts) or differentiation (neuroblastoma cells). By contrast, the amount of phosphorylation appears to diminish in those settings. The considerable abundance and conjectured fibrous structure of AHNAK protein suggest a role in cytoarchitecture, but no function can yet be discerned.
 ...
PMID:The human gene AHNAK encodes a large phosphoprotein located primarily in the nucleus. 838 Nov 20

We have obtained a monoclonal antibody (33A-3D) that specifically recognize desmoyokin, a 680 kDa desmosomal plaque protein that is well characterized in bovine muzzle epidermis. A cDNA clone (DY6, 3693 bp) was isolated by immunoscreening a mouse keratinocyte expression library with 33A-3D, and it was confirmed that DY6 has a partial coding sequence for desmoyokin. DY6 consists of highly homologous repeats about 128 residues long. Furthermore, the 128-residue repeats exhibit a quasi seven-residue substructure, which we believe will adopt an antiparallel beta-sheet structure. Surprisingly, the amino acid sequence showed a significant homology with AHNAK, a newly identified human gene encoding a 700 kDa protein, which was suggested to be down-regulated in neuroblastoma. From its extensive homology, the similarity in both size and structure, and the identical patterns on Southern blot analysis of genomic DNAs, desmoyokin and AHNAK protein are thought to be identical. Although the desmoyokin/AHNAK protein is detected in a variety of cell types at both protein and mRNA levels, its distribution in keratinocytes (associated closely with cell membrane) is quite different from that in cells other than keratinocytes (distributed diffusely in the cytoplasm). These findings suggest that the desmoyokin/AHNAK protein is a ubiquitous molecule with a unique structure and appears to have different distributions (and probably different functions) among different cells.
 ...
PMID:Desmoyokin, a 680 kDa keratinocyte plasma membrane-associated protein, is homologous to the protein encoded by human gene AHNAK. 840 66