Restin: a novel intermediate filament-associated protein highly expressed in the Reed-Sternberg cells of Hodgkin's disease.

Abstract

We have identified a cDNA coding for a protein of 160 kDa which is expressed in in vitro cultured human peripheral blood monocytes. The predicted amino acid sequence contains an alpha‐helical rod domain possessing features characteristic of intermediate filament proteins. However, the immunocytochemical staining pattern, abundance and solubility in Triton X‐100/high salt buffers suggest that this protein is probably only associated with the intermediate filament network and represents a new type of intermediate filament associated protein. In a survey of normal, inflammatory and human tumour tissue samples, this protein, which we have named restin, was found to be highly expressed in Reed‐Sternberg cells, the tumoral cells diagnostic for Hodgkin's disease. We suggest that restin overexpression may be a contributing factor in the progression of Hodgkin's disease.

Hodgkin and Reed-Sternberg cell–associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells

“…According to this view, macropinosomes not associated with CLIP-170 could become excluded from the lysosome transport pathway and deliver their solutes to MIIC compartments or, alternatively, back to the cell surface. Our observation of high-level expression of CLIP-170/restin in DCs is also consistent with the data described by Bilbe et al 14 for restin. Restin was originally detected by a monoclonal antibody raised against the U937 cell line, which is derived from a case of malignant histiocytosis, a clinical entity thought to be a malignant proliferation of cells of histiocytic or Langerhans cell lineages.…”

“…A Chinese hamster ovary (CHO) cell line transformed with a nearly fulllength restin cDNA 14 was kindly provided by Dr Juergen Brueggen. All cell lines were maintained in RPMI 1640 medium (HyClone, Cramlington, United Kingdom) supplemented with 2 mM L-glutamine, 1% pyruvate, streptomycin/penicillin, and 10% fetal calf serum (FCS; PAA Laboratories, Linz, Austria).…”

“…[14][15][16] Significant expression in normal cells was not described. Restin differs from CLIP-170 merely by the insertion of a 35-amino acid stretch located in the center of the molecule and is encoded by a differentially spliced exon flanked by large introns.…”

Crystal Structure of the Cytoskeleton-associated Protein Glycine-rich (CAP-Gly) Domain

“…The CAP-Gly domain was first identified by comparing CLIP-170 (or restin), a filament-associated protein abundant in the tumoral cells characteristic for Hodgkin's disease (31), with other proteins known to be cytoskeleton-associated proteins (5). Recently, this motif of three repeats was also found in the familial cylindromatosis tumor suppressor gene CYLD (32).…”

Cell fusion is not involved in the generation of giant cells in the Hodgkin‐Reed Sternberg cell line L1236

“…Second, H-RS cells express an abnormal phenotype similar to dendritic cells with a lack of B-cell-associated markers in most cases. More recently, molecular studies revealed that in some cases H-RS cells express molecules like Restin [1,2], Fascin [3], or TARC [4], which are typically found on myeloid/monocytic cells. Furthermore, absence of Ig gene transcription is a hallmark of H-RS cells.…”