Browsing by Subject "Ubiquitin"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Open Access
    Changes in spatio-temporal localization of tripeptidyl peptidase II (TPPII) in murine colon adenocarcinoma cells during aggresome formation: a microscopy study based on a novel fluorescent proteasome inhibitor
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Bialy, L.P.; Kuckelkorn, U.; Henklein, P.; Fayet, J.; Wilczyński, G.M.; Kaminski, A.; Mlynarczuk Bialy, I.
    Extralysosomal proteolysis is a multistep process involving the Ubiquitin- Proteasome System (UPS) and supplementary peptidases. Tripeptidyl peptidase II (TPPII) is the most extensively characterized enzyme, supplementing and sometimes substituting for proteasomal functions. In response to proteasome inhibition, polyubiquitinated proteins acting as proteasome substrates aggregate with proteasomes and form aggresomes. Several proteasome inhibitors are used as anti-cancer drugs. Thus, in our study, we used a novel fluorescenttagged proteasome inhibitor BSc2118 to induce aggresome formation in C26 murine colon adenocarcinoma cells. It allowed us to obtain effective, inhibitor-based, proteasome staining in vivo. This method has been validated by standard post-fixed indirect immunostaining and also allowed coimmunodetection of TPPII and polyubiquitinated proteins under laser scanning confocal microscopy. We found that in the absence of the inhibitor, TPPII is diffusely dispersed within the cytoplasm of C26 cells. The proteasome and ubiquitin-rich perinuclear region failed to display enhanced TPPII staining. However, when proteasome function was impaired by the inhibitor, TPPII associated more closely with both the proteasome and polyubiquitinated proteins via TPPII recruitment to the perinuclear region and subsequently into emerging aggresomal structures. Furthermore, we have demonstrated the dynamic recruitment of TPPII into the developing aggresome: TPPII in the early aggresome was dispersed within the central part but subsequently aggregated on the surface of this structure. In the mature aggresome of C26 cells TPPII formed a spherical mantle, which surrounded the round core containing proteasomes and polyubiquitinated proteins. Our morphological data indicate that TPPII displays spatial localization with proteasomes especially upon proteasome inhibition in aggresomes of C26 cells.
  • Thumbnail Image
    Publication
    Open Access
    CSN6: a promising target for cancer prevention and therapy
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Hou, Jianbing; Cui, Hongjuan
    CSN6 has recently received increased attention as a multifunctional protein involved in protein stability. CSN6 plays an important role in controlling cellular proliferation, apoptosis and metastasis, modulating signal transduction, as well as regulating DNA damage and repair. Most studies have demonstrated that CSN6 is significantly upregulated in human malignant tumors such as cervical cancer, papillary thyroid cancer, colorectal cancer, breast cancer, lung adenocarcinoma, and glioblastoma, and its expression is usually correlated with poor prognosis. In this review, we summarize recent available findings regarding the oncogenic role of CSN6 in tumors, and provide a better understanding of CSN6 function at the molecular level and its potential therapeutic implications in combating human cancers
  • Thumbnail Image
    Publication
    Open Access
    The role of the proteasome in cellular protein degradation
    (Murcia : F. Hernández, 1994) Driscoll, J.
    Eukaryotic cells contain a major intracellular proteolytic activity known as the proteasome. The proteasome is a strongly conserved cylindrical structure of high molecular weight (650 kDa, -20 S) and desmonstrates multiple endopeptidase activities. The general structural, biochemical and genetic features of the proteasonie are conserved from archaebacteria through yeast to humans. This structure fulfills an essential role by functioning as the proteolytic core of a 26 S multienzyme complex responsible for the energydependent degradation of ubiquitinated proteins. The bulk of intracellular proteolysis appears to be through the ubiquitin-dependent pathway. Incorporation of the proteasome into the 26 S niultienzyme complex appears to confer both a specificity for ubiquitinated proteins as well as a nieans to tightly regulate proteolytic activity. Thus, one function of the proteasome is required for the degradation of either abnormal or certain regulatory proteins by the ubiquitin pathway. Proteasoine subunits appear to be encoded by a related gene family as defined by extensive sequence similarities. The gene products are confined to either of two general classes: a-type which appear to be structural and 8-type which may be catalytic. Genes encoding at least two proteasome subunits map to the Ma-jor Histocompatibility Complex. Accurnulating evidence points to the proteasome (or a specialized form) participatirig in the cytosolic degradation of these viral proteins upon cellular infection. Through a previously unforseen mechanisin. it appears that the products from the digestion of the viral proteins may be rescued from further digestion to amino acids and shuttled from the cytoplasm through the endoplasniic reticulum to the cell surface where they serve as antigenic peptides for recognition by the immune system. The proteasome may have been recruited by the immune system to serve as the cytosolic activity responsible for generating these antigenic peptides. The proteasome may function in the ubiquitindependent degradation of not only certain self-proteins but may fulfill a second essential role in the degradation of proteins originating from viral infection