Efficient inhibition of macrophage TNF‐α production upon targeted delivery of K48R ubiquitin

Antonelli, A.; Crinelli, Rita; Bianchi, Marzia; Cerasi, Aurora; Gentilini, Lucia; Serafini, Giordano; Magnani, Mauro

doi:10.1046/j.1365-2141.1999.01202.x

Cited by 21 publications

(9 citation statements)

References 31 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To test this hypothesis, we constructed an N-terminal Flag-tagged and C-terminal ubiquitin-fused WT and K124R mutant CENP-A (Figures 4A and 4B). To prevent ubiquitin-fused CENP-A protein from potential polyubiquitylation, we also used the monoubiquitin mutant Ub (K48R), which has lost a major site for polyubiquitylation (Antonelli et al, 1999; Codomo et al, 2014; Thrower et al, 2000). These constructs allowed us to study the role of CENP-A monoubiquitylation.…”

Section: Resultsmentioning

confidence: 99%

CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere

et al. 2015

View full text Add to dashboard Cite

SUMMARY CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromo-some segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A ubiquitylation on lysine 124 (K124) and CENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres and the interaction with HJURP, indicating that “signaling” ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.

show abstract

Section: Resultsmentioning

confidence: 99%

CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere

et al. 2015

View full text Add to dashboard Cite

show abstract

“…We have proved that this is true both in vitro and in vivo and that new compounds can also be designed, synthesized and delivered using erythrocytes as carriers. 14,[15][16][17][18] Among peptides interesting results were obtained in our laboratory by the delivery of a ubiquitin analogue 19 ( Figure 3). This peptide is stable in the erythrocytes and efficiently competes with endogenous ubiquitin in macrophages.…”

Section: Erythrocytes As Drug-targeting Systemmentioning

confidence: 88%

Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides

et al. 2002

View full text Add to dashboard Cite

An important determinant for the success of every new therapy is the ability to deliver the molecules of interest to the target cells or organ. This selective delivery is even Erythrocytes as drug delivery systemsThe selective delivery of new therapeutic agents to target cells or organs is an important challenge in every clinical approach where peptides, oligonucleotides and/or genes are used.1 These molecules, although specific, do not easily cross the cell membranes, are usually not very stable in biological fluids and, because of their production costs, should be used in low amounts. The delivery of genes is usually achieved by viral vectors.2-5 The delivery of oligonucleotides and peptides is instead mediated by coupling or entrapping these therapeutics to, or in a carrier system that has a significant affinity for one or more cell types within the body. A number of attempts have been made to improve the targeting of drugs by engineering the properties of the carrier system. Examples include the use of Tat, VP22, etc. engineered peptides 6,7 or the development of drugs conjugated to ligands specific for receptors known to have a selective cell distribution. [8][9][10][11] Although these delivery systems are very interesting, they suffer a number of limitations including the limited number of molecules delivered and potential adverse effects.Based on these considerations we have developed a cellular drug delivery system which is based on the use of autologous erythrocytes. The carrier system is totally

show abstract

“…Activation of NF-‹ Bdependent events by Leishmania is not surprising because several immune functions modulated by this infection (e.g. TNF- § , PGE2) are known to involve NF-‹ B activation [32][33][34].…”

Section: Signaling Events In Viable Motheaten Mice During Leishmania mentioning

confidence: 99%