| First Author | Somlapura M | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 12 | PubMed ID | 34207662 |
| Mgi Jnum | J:313736 | Mgi Id | MGI:6751110 |
| Doi | 10.3390/ijms22126227 | Citation | Somlapura M, et al. (2021) Different Roles of p62 (SQSTM1) Isoforms in Keratin-Related Protein Aggregation. Int J Mol Sci 22(12) |
| abstractText | p62/Sequestosome-1 (p62) is a multifunctional adaptor protein and is also a constant component of disease-associated protein aggregates, including Mallory-Denk bodies (MDBs), in steatohepatitis and hepatocellular carcinoma. We investigated the interaction of the two human p62 isoforms, p62-H1 (full-length isoform) and p62-H2 (partly devoid of PB1 domain), with keratins 8 and 18, the major components of MDBs. In human liver, p62-H2 is expressed two-fold higher compared to p62-H1 at the mRNA level and is present in slightly but not significantly higher concentrations at the protein level. Co-transfection studies in CHO-K1 cells, PLC/PRF/5 cells as well as p62(-) total-knockout and wild-type mouse fibroblasts revealed marked differences in the cytoplasmic distribution and aggregation behavior of the two p62 isoforms. Transfection-induced overexpression of p62-H2 generated large cytoplasmic aggregates in PLC/PRF/5 and CHO-K1 cells that mostly co-localized with transfected keratins resembling MDBs or (transfection without keratins) intracytoplasmic hyaline bodies. In fibroblasts, however, transfected p62-H2 was predominantly diffusely distributed in the cytoplasm. Aggregation of p62-H2 and p62DeltaSH2 as well as the interaction with K8 (but not with K18) involves acquisition of cross-beta-sheet conformation as revealed by staining with luminescent conjugated oligothiophenes. These results indicate the importance of considering p62 isoforms in protein aggregation disease. |
