Proteasome inhibitors: valuable new tools for cell biologists

Lee, Do Hee; Goldberg, Alfred L.

doi:10.1016/s0962-8924(98)01346-4

Cited by 1,347 publications

(1,105 citation statements)

References 47 publications

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“…Indeed, all reagents precluding the AIF mitochondrial processing (including proteasome inhibitors) inhibit two major families of cystein proteases: calpains and cathepsins. [16][17][18] However, as calpains are inactive enzymes in the Atr calcium-depleted system (Figure 1c), our results point toward a cathepsin implication in Ca 2 þ -independent AIF processing. Thus, we looked for an individual cathepsin protease integrating the results presented above.…”

mentioning

confidence: 58%

Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release

Yuste¹,

Moubarak²,

Delettre³

et al. 2005

Cell Death Differ

121

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mentioning

confidence: 58%

Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release

Yuste¹,

Moubarak²,

Delettre³

et al. 2005

Cell Death Differ

121

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“…While degradation of proteins can occur by various systems in both fractions [39], it is possible that one may be preferentially stabilized leading to a differential level of degradation in that compartment. To determine if this is the case with EKLF, MEL cells were treated with MG132, a potent pharmacological inhibitor of the 26S proteasome, prior to fractionation [40]. As we have previously observed, inhibition of the proteasome with MG132 leads to an increase in the accumulated steady state levels of EKLF in unfractionated MEL cells, where its normal half-life is <3 hours [25].…”

Section: The Eklf Nuclear/cytoplasmic Ratio Is Not Altered By a Variementioning

confidence: 98%

Non-random subcellular distribution of variant EKLF in erythroid cells

Quadrini¹,

Gruzglin²,

Bieker³

2008

Experimental Cell Research

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EKLF protein plays a prominent role during erythroid development as a nuclear transcription factor. Not surprisingly, exogenous EKLF quickly localizes to the nucleus. However, using two different assays we have unexpectedly found that a substantial proportion of endogenous EKLF resides in the cytoplasm at steady state in all erythroid cells examined. While EKLF localization does not appear to change during either erythroid development or terminal differentiation, we find that the protein displays subtle yet distinct biochemical and functional differences depending on which subcellular compartment it is isolated from, with PEST sequences possibly playing a role in these differences. Localization is unaffected by inhibition of CRM1 activity and the two populations are not differentiated by stability. Heterokaryon assays demonstrate that EKLF is able to shuttle out of the nucleus although its nuclear re-entry is rapid. These studies suggest there is an unexplored role for EKLF in the cytoplasm that is separate from its well-characterized nuclear function.

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“…(39,40) SOX9-induced RUNX2 degradation is ubiquitin-proteasome-independent Since RUNX2 is degraded through the ubiquitin-proteasome pathway, (22,25,41) we hypothesized that SOX9 promoted RUNX2 degradation through this mechanism. To test this hypothesis, the proteasome inhibitor MG132 (42) was applied to HEK293 cells in which we overexpressed RUNX2, SOX9, or both. We found that MG132 stabilized RUNX2 when expressed alone (compare lane 6 with lane 2 in Fig.…”

Section: Runx2 Inhibits Sox9 Transactivity During Chondrogenesis In Amentioning

confidence: 99%

SOX9 determines RUNX2 transactivity by directing intracellular degradation

Cheng

Genever

2010

Journal of Bone and Mineral Research

133

112

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Mesenchymal stem cell differentiation is controlled by the cooperative activity of a network of signaling mechanisms. Among these, RUNX2 and SOX9 are the major transcription factors for osteogenesis and chondrogenesis, respectively. Their expression is overlapped both temporally and spatially during embryogenesis. Here we have demonstrated that RUNX2 and SOX9 physically interact in intact cells and have confirmed that SOX9 can inhibit the transactivation of RUNX2. In addition, RUNX2 exerts reciprocal inhibition on SOX9 transactivity. In analyses of the mechanism by which SOX9 regulated RUNX2 function, we demonstrated that SOX9 induced a dosedependent degradation of RUNX2. Although RUNX2 is normally degraded by the ubiquitin-proteasome pathway, we found that SOX9-mediated degradation was proteasome-independent but phosphorylation-dependent and required the presence of the RUNX2 Cterminal domain, which contains a nuclear matrix targeting sequence (NMTS). Furthermore, SOX9 was able to decrease the level of ubiquitinated RUNX2 and direct RUNX2 to the lysosome for degradation. SOX9 also preferentially directed b-catenin, an intracellular mediator of canonical Wnt signaling, for lysosomal breakdown. Consequently, the mechanisms by which SOX9 regulates RUNX2 function may underlie broader signaling pathways that can influence osteochondrogenesis and mesenchymal fate. ß

show abstract

Proteasome inhibitors: valuable new tools for cell biologists

Cited by 1,347 publications

References 47 publications

Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release

Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release

Non-random subcellular distribution of variant EKLF in erythroid cells

SOX9 determines RUNX2 transactivity by directing intracellular degradation

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