The ubiquitin-proteasome pathway of intracellular proteolysis

Doherty, Fergus J.; Dawson, Simon; Mayer, R. John

doi:10.1042/bse0380051

Cited by 72 publications

(52 citation statements)

References 33 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ubiquitin-proteasome pathway (UPP) is the major intracellular system for extralysosomal protein degradation [47,48]. In the present study, we chose to inhibit 20S proteasome.…”

Section: Discussionmentioning

confidence: 99%

The involvement of glycogen synthase kinase‐3 and protein phosphatase‐2A in lactacystin‐induced tau accumulation

et al. 2006

View full text Add to dashboard Cite

Here, we demonstrated that lactacystin inhibited proteasome dose-dependently in HEK293 cells stably expressing tau. Simultaneously, it induces accumulation of both non-phosphorylated and hyperphosphorylated tau and decreases the binding of tau to the taxol-stabilized microtubules. Lactacystin activates glycogen synthase kinsase-3 (GSK-3) and decreases the phosphorylation of GSK-3 at serine-9. LiCl inhibits GSK-3 and thus reverses the lactacystin-induced accumulation of the phosphorylated tau. Lactacystin also inhibits protein phosphase-2A (PP-2A) and it significantly increases the level of inhibitor 1 of PP-2A. These results suggest that inhibition of proteasome by lactacystin induces tau accumulation and activation of GSK-3 and inhibition of PP-2A are involved.

show abstract

“…Ubiquitin-proteasome pathway (UPP) is the major intracellular system for extralysosomal protein degradation [47,48]. In the present study, we chose to inhibit 20S proteasome.…”

Section: Discussionmentioning

confidence: 99%

The involvement of glycogen synthase kinase‐3 and protein phosphatase‐2A in lactacystin‐induced tau accumulation

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Proteins degraded by the ubiquitin-proteasome pathway include cyclins and other regulators of the cell cycle, and transcription factors. 27 Protein degradation is thus a mechanism to regulate the concentration of many regulatory proteins.…”

Section: Genes Involved In Protein Degradationmentioning

confidence: 99%

T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34+CD38−CD7+ common lymphoid progenitors expressing lymphoid-specific genes

et al. 2006

View full text Add to dashboard Cite

Hematopoietic stem cells in the bone marrow (BM) give rise to all blood cells. According to the classic model of hematopoiesis, the differentiation paths leading to the myeloid and lymphoid lineages segregate early. A candidate 'common lymphoid progenitor' (CLP) has been isolated from CD34 þ CD38 À human cord blood cells based on CD7 expression. Here, we confirm the B-and NK-differentiation potential of CD34 þ CD38 À CD7 þ cells and show in addition that this population has strong capacity to differentiate into T cells. As CD34 þ CD38 À CD7 þ cells are virtually devoid of myeloid differentiation potential, these cells represent true CLPs. To unravel the molecular mechanisms underlying lymphoid commitment, we performed genome-wide gene expression profiling on sorted CD34 þ CD38 À CD7 þ and CD34 þ CD38 À CD7 À cells. Interestingly, lymphoid-affiliated genes were mainly upregulated in the CD7 þ population, while myeloid-specific genes were downregulated. This supports the hypothesis that lineage commitment is accompanied by the shutdown of inappropriate gene expression and the upregulation of lineage-specific genes. In addition, we identified several highly expressed genes that have not been described in hematopoiesis before.

show abstract

“…The ubiquitin/proteasome pathway controls the turnover of products of many oncogenes and tumor suppressor genes and thus plays a major role in cancer development (1)(2)(3)(4)(5). Recently, a number of ubiquitin-related proteins have also been found in eukaryotic cells.…”

mentioning

confidence: 99%

Regulation of Smad4 Sumoylation and Transforming Growth Factor-β Signaling by Protein Inhibitor of Activated STAT1

Liang

Melchior

Feng

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The tumor suppressor, Smad4/DPC4, is a common signal transducer in transforming growth factor-␤ (TGF-␤) signaling. In this study, we demonstrated that the protein inhibitor of activated STAT1 (PIAS1) regulates the signaling potential of Smad4 through a sumoylation-dependent mechanism. PIAS1 was shown to be an E3 ligase for Smad4 sumoylation in vitro and in vivo. The ubiquitin/proteasome pathway controls the turnover of products of many oncogenes and tumor suppressor genes and thus plays a major role in cancer development (1-5). Recently, a number of ubiquitin-related proteins have also been found in eukaryotic cells. These proteins, including the small ubiquitinlike modifier 1 (SUMO1), 1 utilize a conjugation system that is similar to ubiquitination (6, 7). In particular, SUMO is activated in an ATP-dependent manner by an E1 enzyme consisting of the Aos1/Uba2 heterodimer and then transferred to the SUMO-conjugating E2 enzyme Ubc9 and subsequently ligated to the substrate. In contrast to ubiquitination, SUMO1 modifications of target proteins do not promote their degradation. Furthermore, SUMO1 modification reduces ubiquitination of tumor suppressor Smad4 (8) and may also preclude ubiquitination of I B (9). The functional consequences of SUMO1 modification vary depending on the target. For example, SUMO1 conjugation is necessary for RanGAP1 localization to the nuclear pore complex (10, 11), for nuclear import of the transcription corepressor CtBP (12), and for localization of promyelocytic leukemia to the nuclear bodies (13). For many other proteins, their covalent modifications by SUMO1 modulate their biological activities (7, 14 -19).Substrates of SUMO conjugation often contain a tetrapeptide motif, i.e. KX(D/E) (where is hydrophobic and X is any amino acid). Structural analysis of the complex between Ubc9 and its substrate, RanGAP1, demonstrates clearly how the motif is specifically recognized by Ubc9 and elucidates nicely why RanGAP1 sumoylation may not depend on an E3 ligase (20). However, more recent reports support the presence of E3 enzymes for sumoylation (21-24). In particular, a family of SUMO E3 ligases, termed protein inhibitors of activated STAT (PIAS), has recently been discovered (21,22). The PIAS protein family consists of five members: PIAS1, PIAS3, PIASx␣, PIASx␤, and PIASy. PIAS1 and PIAS3 were originally shown to interact with STAT1 and STAT3, respectively, and inhibit their functions (25,26). Recently other PIAS proteins have been shown to function as coregulators for nuclear receptors (27-32). The first demonstration of a mammalian PIAS protein as a SUMO E3 ligase was shown in the involvement of PIAS1 in p53 sumoylation (33). PIAS proteins resemble the RING-class ubiquitin E3 ligases and bind to Ubc9 through the RING finger domain (34). The RING finger domain is highly conserved among PIAS proteins and is supported by the observation that, similar to PIAS1, PIASx␤ also promotes the sumoylation of CtBP (12), p53, and c-Jun (35). Although PIASx␣ binds to the androgen receptor through the RING ...

show abstract

The ubiquitin-proteasome pathway of intracellular proteolysis

Cited by 72 publications

References 33 publications

The involvement of glycogen synthase kinase‐3 and protein phosphatase‐2A in lactacystin‐induced tau accumulation

The involvement of glycogen synthase kinase‐3 and protein phosphatase‐2A in lactacystin‐induced tau accumulation

T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34+CD38−CD7+ common lymphoid progenitors expressing lymphoid-specific genes

Regulation of Smad4 Sumoylation and Transforming Growth Factor-β Signaling by Protein Inhibitor of Activated STAT1

Contact Info

Product

Resources

About