Efficient Cleavage of Bid and Procaspase-7 by Caspase-2 at Lower pH

Karki, Pratap; Dahal, Giri Raj; Shin, Song Yub; Lee, Jung Sup; Cho, Byungyun; Park, Il‐Seon

doi:10.2174/092986608786071193

Cited by 8 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent reports confirmed this finding using purified caspase-2 [131,150,151]. It was recently reported that four times more caspase-2 (in its preferred pH 6.75 buffer) than caspase-8 was required to cleave purified Bid [145]. This finding was consistent with less quantitative prior data implying that Bid cleavage by caspase-8 was more efficient than by caspase-2 [131,[149][150][151].…”

Section: Protein Substratessupporting

confidence: 64%

“…Cleavage efficiencies have only been published for two substrates (Table 2). In vitro, caspase-2 was recently determined to exhibit maximal activity against protein substrates in low pH buffers (5.5-7.0) lacking salt [145]. Interestingly, peptide substrates were most efficiently cleaved in neutral or only slightly basic buffers [145,146].…”

Section: Substrates and Specificitymentioning

confidence: 99%

“…Although initial data implied that caspase-2 was unable to digest other caspase precursors [157], evidence has been published suggesting that it could process and activate pro-caspase-7 [131]. Using the low pH buffer in which caspase-2 most efficiently cleaves protein substrates, pro-caspase-7 was recently confirmed to be sensitive to caspase-2-dependent proteolysis, although higher concentrations of caspase-2 than caspase-8 were required to achieve similar cleavage [145].…”

Section: Protein Substratesmentioning

confidence: 99%

See 2 more Smart Citations

Caspase-2: controversial killer or checkpoint controller?

2009

View full text Add to dashboard Cite

The caspases are an evolutionarily conserved family of cysteine proteases, with essential roles in apoptosis or inflammation. Caspase-2 was the second caspase to be cloned and it resembles the prototypical nematode caspase CED-3 more closely than any other mammalian protein. An absence of caspase-2-specific reagents and the subtle phenotype of caspase-2-deficient mice have hampered definition of the physiological role of caspase-2 and identification of factors regulating its activity. Although some data implicate caspase-2 in apoptotic pathways, a link with apoptosis has been less firmly established for caspase-2 than for some other caspases. Emerging evidence suggests that caspase-2 regulates the cell cycle and may act as a tumour suppressor. This article critically reviews the current state of knowledge regarding the biochemistry and biology of this controversial caspase.

show abstract

Section: Protein Substratessupporting

confidence: 64%

Section: Substrates and Specificitymentioning

confidence: 99%

Section: Protein Substratesmentioning

confidence: 99%

See 1 more Smart Citation

Caspase-2: controversial killer or checkpoint controller?

2009

View full text Add to dashboard Cite

show abstract

“…Cleavage of human Mdm2 by caspase-2 has been reported to stabilize p53 and might contribute to the increased p53-dependent drug resistance of non-small cell lung carcinoma cell lines (27). Caspase-2 does not cleave (30) or proteolytically activate executioner caspases (31), with the exception of cleaving caspase-7 at pH 2.0, which is most likely not relevant in vivo (32).…”

mentioning

confidence: 99%

Degradomics Reveals That Cleavage Specificity Profiles of Caspase-2 and Effector Caspases Are Alike

Wejda

Impens

Takahashi

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:To study the potential role of caspase-2, we determined its cleavage site specificity and compared it with that of caspase-3 and -7. Results: N-terminal COFRADIC analysis of native proteomes revealed that caspase-2, -3, and -7 have overlapping specificities. Conclusion: Caspase-2, -3, and -7 share nearly indistinguishable cleavage site specificity. Significance: This finding suggests that caspase-2 has a proapoptotic function.

show abstract

“…28 Hence, to exclude the possibility that the presence of active recombinant caspase-2 may lead to the activation of downstream effector caspases that could cleave additional proteins in the cell lysates, we examined the processing of caspase-3 and -7, as well as the activities of these caspases in recombinant caspase-2-treated cytosol fractions. Western blot analysis of these lysates revealed processing of endogenous caspase-2, whereas processing of endogenous caspase-3 or -7 was not detected (Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

Caspase-2 promotes cytoskeleton protein degradation during apoptotic cell death

Vakifahmetoglu-Norberg

Norberg

Perdomo

et al. 2013

Cell Death Dis

View full text Add to dashboard Cite

The caspase family of proteases cleaves large number of proteins resulting in major morphological and biochemical changes during apoptosis. Yet, only a few of these proteins have been reported to selectively cleaved by caspase-2. Numerous observations link caspase-2 to the disruption of the cytoskeleton, although it remains elusive whether any of the cytoskeleton proteins serve as bona fide substrates for caspase-2. Here, we undertook an unbiased proteomic approach to address this question. By differential proteome analysis using two-dimensional gel electrophoresis, we identified four cytoskeleton proteins that were degraded upon treatment with active recombinant caspase-2 in vitro. These proteins were degraded in a caspase-2-dependent manner during apoptosis induced by DNA damage, cytoskeleton disruption or endoplasmic reticulum stress. Hence, degradation of these cytoskeleton proteins was blunted by siRNA targeting of caspase-2 and when caspase-2 activity was pharmacologically inhibited. However, none of these proteins was cleaved directly by caspase-2. Instead, we provide evidence that in cells exposed to apoptotic stimuli, caspase-2 probed these proteins for proteasomal degradation. Taken together, our results depict a new role for caspase-2 in the regulation of the level of cytoskeleton proteins during apoptosis.

show abstract

Efficient Cleavage of Bid and Procaspase-7 by Caspase-2 at Lower pH

Cited by 8 publications

References 0 publications

Caspase-2: controversial killer or checkpoint controller?

Caspase-2: controversial killer or checkpoint controller?

Degradomics Reveals That Cleavage Specificity Profiles of Caspase-2 and Effector Caspases Are Alike

Caspase-2 promotes cytoskeleton protein degradation during apoptotic cell death

Contact Info

Product

Resources

About