Relationship between the Expression Level of PSMD11 and Other Proteasome Proteins with the Activity of Ricin and Viscumi
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HEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
Relationship between the Expression Level of PSMD11 and Other Proteasome Proteins with the Activity of Ricin and Viscumin D. V. Maltsevaa,b,c,*, M. P. Raigorodskayab, O. V. Tikhonovad, E. N. Knyazeva,**, and E. A. Tonevitskye Presented by Academician A.V. Lisitsa Received March 23, 2020; revised March 25, 2020; accepted March 27, 2020
Abstract –The role of proteasome proteins and proteins of the ERAD system in the cytotoxicity of type II ribosome-inactivating proteins ricin and viscumin was investigated. For this, the cell line of colorectal adenocarcinoma HT29, as well as the HT29-sh002 line obtained on its basis, were used. On the basis on the proteome analysis of these lines and the estimation of the proportion of inactivated ribosomes, it was shown that the contribution of the proteasome to the degradation of the catalytic subunits of toxins is different. The role of the Cdc37 co-chaperone in maintaining the stability of A subunit of viscumin in the cytoplasm is shown. Keywords: Cdc37, ERAD, HT29, MLI, PSMD11, degradation, proteasome, ribosome inactivating protein, ricin, viscumin DOI: 10.1134/S1607672920040080
A characteristic feature of type II ribosome-inactivating proteins (RIP-II) is the presence of A and B subunits connected through a disulfide bond [1]. The B subunit ensures the binding of RIP-II to the cell membrane and penetration into the endoplasmic reticulum (ER) via retrograde transport. The A subunit ensures the toxic effect of RIP-II, exhibits catalytic N-glycosidase activity, and irreversibly modifies ribosomes. For the realization of the toxic effect, the disulfide bond connecting the subunits must be reduced in ER. In this case, the A subunit partially unfolds, and the flexibility of the protein globule Abbreviations: ERAD, endoplasmic reticulum-associated protein quality control and degradation system, RTA, ricin toxin subunit A, VTA, viscumin toxin subunit A, real-time PCR, polymerase chain reaction with real-time product detection, RIB, type II ribosome-inactivating protein, ER, endoplasmic reticulum.
a Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia b Scientific Research Center Bioclinicum, Moscow, Russia c Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia d Institute of Biomedical Chemistry, Moscow, Russia e Development Fund of the Mendeleev Valley Innovation Science and Technology Center, Moscow, Russia *e-mail: [email protected] **e-mail: [email protected]
increases, which is a signal for its translocation through the ER membrane, mediated by the ERAD system—an ER-associated protein quality control and degradation system [1–3]. The degradation of partially unfolded proteins, endogenous for ER, includes the following main steps: (1) detection and sorting, (2) translocation through the ER membrane and transfer of the protein to the cytoplasm, and (3) degradation in the proteasome. The RIP-II A subunits, unlike the endogenous p
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