Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stumptner, C; Heid, H; Fuchsbichler, A; Hauser, H; Mischinger, HJ; Zatloukal, K; Denk, H.
Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent.
Am J Pathol. 1999; 154(6):1701-1710
Doi: 10.1016/S0002-9440(10)65426-0
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- Führende Autor*innen der Med Uni Graz
- Denk Helmut
- Co-Autor*innen der Med Uni Graz
- Hauser Hubert
- Mischinger Hans-Jörg
- Stumptner Cornelia
- Zatloukal Kurt
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- Abstract:
- Intracytoplasmic hyaline bodies (IHBs) resemble inclusions in hepatocellular carcinoma cells, which so far have escaped further characterization. A relationship to Mallory bodies was suggested on the basis of light microscopy and filamentous ultrastructure. A hepatocellular carcinoma containing numerous IHBs was studied. Our studies revealed immunoreactivity of IHBs with the monoclonal antibodies SMI 31 and MPM-2, which recognize hyperphosphorylated epitopes present on paired helical filaments in Alzheimer's disease brains (SMI 31) or on diverse proteins hyperphosphorylated by mitotic kinases in the M-phase of the cell cycle (MPM-2). One- and two-dimensional gel electrophoresis of tumor extracts followed by immunoblotting with SMI 31 and MPM-2 antibodies revealed a major immunoreactive protein with an apparent molecular weight between 62 and 65 kd, which was resolved into several highly acidic (pH 4.5) protein components in two-dimensional gels. This protein was undetectable in non-neoplastic liver tissue. Sequence analysis identified the SMI 31 and MPM-2 immunoreactive material as p62, indicating that p62 is a major constituent of IHBs. p62 is an only recently discovered protein that is a phosphotyrosine-independent ligand of the SH2 domain of p56(lck), a member of the c-src family of cytoplasmic kinases. Moreover, p62 binds ubiquitin and may act as an adapter linking ubiquitinated species to other proteins. These features suggest a role of p62 in signal transduction and possibly also carcinogenesis. IHBs observed in the hepatocellular carcinoma cells presented are the first indications of a role of p62 in disease.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptor Proteins, Signal Transducing -
- Amino Acid Sequence -
- Antibodies, Monoclonal -
- Blotting, Western -
- Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - ultrastructure
- Carrier Proteins - immunology Carrier Proteins - metabolism
- Electrophoresis, Polyacrylamide Gel -
- Fatal Outcome -
- Fluorescent Antibody Technique, Indirect -
- Humans -
- Hyalin - metabolism Hyalin - ultrastructure
- Immediate-Early Proteins - immunology Immediate-Early Proteins - metabolism
- Immunohistochemistry -
- Inclusion Bodies - metabolism Inclusion Bodies - ultrastructure
- Liver Neoplasms - metabolism Liver Neoplasms - pathology Liver Neoplasms - ultrastructure
- Male -
- Microscopy, Electron -
- Middle Aged -
- Molecular Sequence Data -
- Proteins -
- Sequence Analysis -