Interaction of Hsp90 with Ribosomal Proteins Protects from Ubiquitination and Proteasome-dependent Degradation

Kim, Tae Sung; Jang, Chang-Young; Kim, Hag Dong; Lee, Jae Yung; Ahn, Byung Yoon; Kim, Joon

doi:10.1091/mbc.e05-08-0713

Cited by 97 publications

(85 citation statements)

References 46 publications

(45 reference statements)

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“…Yvh1 phosphatase activity has been demonstrated in vitro (Guan et al 1992), and we can speculate that Yvh1 phosphatase activity may have a regulatory function in vivo that affects ribosomal assembly and perhaps synthesis of specific proteins under certain conditions. The ubiquitin-proteasome system also participates in ribosome biogenesis (Kim et al 2006;Stavrena et al 2006). Although many ubiquitin ligases have RING finger domains (Fang et al 2003), there is no evidence at present for a role for Yvh1 in ubiquitination: no significant difference in the profile of ubiquitinated proteins was observed in wild-type and yvh1D cells ( Figure 2C).…”

Section: Discussionmentioning

confidence: 99%

A Mutant Plasma Membrane Protein Is Stabilized Upon Loss of Yvh1, a Novel Ribosome Assembly Factor

Liu

Chang

2009

Genetics

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Pma1-10 is a mutant plasma membrane ATPase defective at the restrictive temperature in stability at the cell surface. At 37°, Pma1-10 is ubiquitinated and internalized from the plasma membrane for degradation in the vacuole. YVH1, encoding a tyrosine phosphatase, is a mutant suppressor of pma1-10 ; in the absence of Yvh1, Pma1-10 remains stable at the plasma membrane, thereby permitting cells to grow. The RING finger domain of Yvh1, but not its phosphatase domain, is required for removal of mutant Pma1-10 from the plasma membrane. Yvh1 is a novel ribosome assembly factor: in yvh1D cells, free 60S and 80S ribosomal subunits are decreased, free 40S subunits are increased, and half-mer polysomes are accumulated. Pma1-10 is also stabilized by deletion of 60S ribosomal proteins Rpl19a and Rpl35a. We propose that changes in ribosome biogenesis caused by loss of Yvh1 or specific ribosomal proteins have effects on the plasma membrane, perhaps by producing specific translational changes.

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Section: Discussionmentioning

confidence: 99%

A Mutant Plasma Membrane Protein Is Stabilized Upon Loss of Yvh1, a Novel Ribosome Assembly Factor

Liu

Chang

2009

Genetics

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“…Cell fractionation and ribosome pelleting Cellular fractionation of the nucleus and cytosol as well as ribosome-pelleting using a sucrose cushion were performed as previously described (Kim et al, 2006(Kim et al, , 2009.…”

Section: Methodsmentioning

confidence: 99%

Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest

2011

Oncogene

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The largest energy consumer in the cell is the ribosome biogenesis whose aberrancy elicits various diseases in humans. It has been recently revealed that p53 induction, along with cell cycle arrest, is related with abnormal ribosome biogenesis, but the exact mechanism still remains unknown. In this study, we have found that aberrant ribosome biogenesis activates two parallel cellular pathways, c-Myc and ASK1/p38, which result in p53 induction and G1 arrest. The c-Myc stabilizes p53 by rpL11-mediated HDM2 inhibition, and ASK1/p38 activates p53 by phosphorylation on serine 15 and 33. Our studies demonstrate the relationship between these two pathways and p53 induction. The changes caused by impaired ribosomal stress, such as p53 induction and G1 arrest, were completely disappeared by inhibition of either pathway. These findings suggest a monitoring mechanism of c-Myc and ASK1/p38 against abnormal ribosome biogenesis through controlling the stability and activity of p53 protein.

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“…4). Indeed, it has been reported that the molecular chaperone Hsp90 interacts with ribosomal proteins and thus prevents it from the ubiquitination and proteasome-derived degradation in mammalian cells (39).…”

Section: Gene Expression Profile Showed Similar Patterns Of Ms/ms Anamentioning

confidence: 99%

Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer

Song

Chaerkady

Tan

et al. 2008

Molecular Cancer Therapeutics

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Targeting Hsp90 is an attractive strategy for anticancer therapy because the diversity and relevance of biological processes are regulated by these proteins in most cancers. However, the role and mode of action of Hsp90 inhibitors in pancreatic cancer has not been studied. This study aimed to assess the antitumor activity of the Hsp90 inhibitor, IPI-504, in pancreatic cancer and to determine the biological effects of the agent. In vitro, we show that pharmacologic inhibition of Hsp90 by IPI-504 exerts antiproliferative effects in a panel of pancreatic cancer cells in a dose-and time-dependent manner. In pancreatic cancer xenografts obtained directly from patients with pancreas cancer, the agent resulted in a marked suppression of tumor growth. Although known Hsp90 client proteins were significantly modulated in IPI-504-treated cell line, no consistent alteration of these proteins was observed in vivo other than induction of Hsp70 expression in the treated xenografted tumors. Using a proteomic profiling analysis with isotope tags for relative and absolute quantitation labeling technique, we have identified 20 down-regulated proteins and 42 up-regulated proteins on IPI-504 treatment.tumor growth Identical changes were observed in the expression of the genes coding for these proteins in a subset of proteins including HSPA1B, LGALS3, CALM1, FAM84B, FDPS, GOLPH2, HBA1, HIST1H1C, HLA-B, and MARCKS. The majority of these proteins belong to the functional class of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism. In summary, we show that IPI-504 has potent antitumor activity in pancreatic cancer and identify potential pharmacologic targets using a proteomics and gene expression profiling.

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Interaction of Hsp90 with Ribosomal Proteins Protects from Ubiquitination and Proteasome-dependent Degradation

Cited by 97 publications

References 46 publications

A Mutant Plasma Membrane Protein Is Stabilized Upon Loss of Yvh1, a Novel Ribosome Assembly Factor

A Mutant Plasma Membrane Protein Is Stabilized Upon Loss of Yvh1, a Novel Ribosome Assembly Factor

Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest

Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer

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