Coupling caspase cleavage and ubiquitin–proteasome-dependent degradation of SSRP1 during apoptosis

Landais, Igor; Lee, H; Lu, Hua

doi:10.1038/sj.cdd.4401878

Cited by 12 publications

(18 citation statements)

References 41 publications

(72 reference statements)

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“…For certain substrates removal of a regulatory domain results in their constitutive activation, as in the case of various kinases (11,12). For others, cleavage results in a loss of function, and the resulting fragments are frequently degraded by the 26S proteasome (5)(6)(7)(8)(9)(10). In this study, we found an interaction between caspases and the ubiquitin-proteasome system.…”

Section: Discussionmentioning

confidence: 52%

“…Caspase cleavage can inactivate proteins or generate dominant-negative inhibitors, as in the case of gelsolin, RIP1, and eIF4E-BP1 (4). Moreover, caspase cleavage of numerous substrates, including IRF-3, ErbB2, cyclin E, claspin, SSRP1, and Twist, can enhance their turnover by the proteasome (5)(6)(7)(8)(9)(10). Conversely, caspases can also constitutively activate proteins, particularly kinases such as PKC and Mst1 (11,12), or change the function of a protein altogether, as seen in the conversion of antiapoptotic BCL-2 proteins into proapoptotic BAX-like proteins (13).…”

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confidence: 99%

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Caspase-dependent regulation of the ubiquitin–proteasome system through direct substrate targeting

Yeh¹,

Bratton²

2013

Proc. Natl. Acad. Sci. U.S.A.

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Drosophila inhibitor of apoptosis (IAP) 1 (DIAP1) is an E3 ubiquitin ligase that regulates apoptosis in flies, in large part through direct inhibition and/or ubiquitinylation of caspases. IAP antagonists, such as Reaper, Hid, and Grim, are thought to induce cell death by displacing active caspases from baculovirus IAP repeat domains in DIAP1, but can themselves become targets of DIAP1-mediated ubiquitinylation. Herein, we demonstrate that Grim self-associates in cells and is ubiquitinylated by DIAP1 at Lys136 in an UbcD1-dependent manner, resulting in its rapid turnover. K48-linked ubiquitin chains are added almost exclusively to BIR2-bound Grim as a result of its structural proximity to DIAP1's RING domain. However, active caspases can simultaneously cleave Grim at Asp132, removing the lysine necessary for ubiquitinylation as well as any existing ubiquitin conjugates. Cleavage therefore enhances the stability of Grim and initiates a feed-forward caspase amplification loop, resulting in greater cell death. In summary, Grim is a caspase substrate whose cleavage promotes apoptosis by limiting, in a target-specific fashion, its ubiquitinylation and turnover by the proteasome.

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Section: Discussionmentioning

confidence: 52%

mentioning

confidence: 99%

Caspase-dependent regulation of the ubiquitin–proteasome system through direct substrate targeting

Yeh¹,

Bratton²

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…SSRP1 increased 2.7-fold after IR in the wild type but did not increase significantly in the mutant. Interestingly SSRP1 has been shown to be degraded during apoptosis; it is possible that the lower relative amount of this protein in the mutant versus wild type thymocytes is related to increased apoptosis as a result of the mutation (44). These results suggest that important differences occur in the regulation of transcription between the wild type and p53 K317R thymocytes.…”

Section: Quantitative Analysis Of Ir Effects In P53 K317r Thymocytesmentioning

confidence: 53%

Quantitative Proteomics Analysis of the Effects of Ionizing Radiation in Wild Type and p53K317R Knock-in Mouse Thymocytes

Jenkins

Mazur

Rossi

et al. 2008

Molecular & Cellular Proteomics

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The tumor suppressor protein p53 is a sequence-specific transcription factor that has crucial roles in apoptosis, cell cycle arrest, cellular senescence, and DNA repair. Following exposure to a variety of stresses, p53 becomes posttranslationally modified with concomitant increases in activity and stability. To better understand the role of acetylation of Lys-317 in mouse p53, the effect of ionizing radiation (IR) on the thymocytes of p53 K317R knock-in mice was studied at the global level. Using cleavable ICAT quantitative mass spectrometry, the effect of IR on protein levels in either the wild type or p53 K317R thymocytes was determined. We found 102 proteins to be significantly affected by IR in the wild type thymocytes, including several whose expression has been shown to be directly regulated by p53. When the effects of IR in the wild type and p53 K317R samples were compared, 46 proteins were found to be differently affected (p < 0.05). The p53 K317R mutation has widespread effects on specific protein levels following IR, including the levels of proteins involved in apoptosis, transcription, and translation. Pathway analysis of the differently regulated proteins suggests an increase in p53 activity in the p53 K317R thymocytes as well as a decrease in tumor necrosis factor ␣ signaling. These results suggest that acetylation of Lys-317 modulates the functions of p53 and influences the cross-talk between

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“…Of note, a light band at ϳ50 kDa detected by the polyclonal antibody (Fig. 1A) has been shown to be a cleaved SSRP1 fragment (23). In interphase cells, SSRP1 predominantly localized to the nucleus (Fig.…”

Section: Ssrp1 Colocalizes With Mitotic Mtmentioning

confidence: 99%

“…Also, this heterodimer binds to the protein kinase CK2, forming a specific kinase complex for the tumor suppressor protein p53 (19,20). In addition, SSRP1 acts as a transcriptional coactivator (53), can physically modify chromatin (29), and is cleaved during apoptosis (23). However, the precise biological role of SSRP1 remains unclear, as murine ssrp1 knockouts are lethal at E3.5 (4).…”

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confidence: 99%

Structure-Specific Recognition Protein 1 Facilitates Microtubule Growth and Bundling Required for Mitosis

Zeng

Jin

et al. 2010

Molecular and Cellular Biology

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Tight regulation of microtubule (MT) dynamics is essential for proper chromosome movement during mitosis. Here we show, using mammalian cells, that structure-specific recognition protein 1 (SSRP1) is a novel regulator of MT dynamics. SSRP1 colocalizes with the spindle and midbody MTs, and associates with MTs both in vitro and in vivo. Purified SSRP1 facilitates tubulin polymerization and MT bundling in vitro. Knockdown of SSRP1 inhibits the growth of MTs and leads to disorganized spindle structures, reduction of K-fibers and midbody fibers, disrupted chromosome movement, and attenuated cytokinesis in vivo. These results demonstrate that SSRP1 is crucial for MT growth and spindle assembly during mitosis.Mitosis is the final and critical stage of cell division essential for cell proliferation, embryogenesis, and tumorigenesis. During mitosis, duplicated chromosomes are condensed, aligned, segregated, and equally packed into two daughter cells through cytokinesis (36). These chromosome movements are driven by bipolar spindles working in concert with stabilizing and destabilizing proteins (22). At the core of this mitotic machinery are microtubules (MTs) (22), which consist of polymerized ␣-tubulin/␤-tubulin heterodimers (45). At prometaphase, MT nucleation mediated by a number of spindle assembly factors, such as the ␥-tubulin ring complexes (47), is organized into bipolar arrays of MT bundles of the mitotic spindle that functions to capture, align, and segregate chromosomes in dividing cells (1). Thus, MT polymerization and bundling are necessary for the assembly of the mitotic machinery (22,36,45), although this machinery is dynamic with constant polymerization (rescue) and depolymerization (catastrophe) at the MT plus ends (34). These activities are finely tuned through the balancing action between plus-and minus-end regulators (22).To understand how bipolar MTs are exactly regulated during mitosis, a number of proteins crucial for spindle assembly and midbody formation have been identified (13,21,30,37,38,40). One group of proteins important for spindle assembly is the family of plus-end motor kinesin-5 proteins (2,33,36,43).

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Coupling caspase cleavage and ubiquitin–proteasome-dependent degradation of SSRP1 during apoptosis

Cited by 12 publications

References 41 publications

Caspase-dependent regulation of the ubiquitin–proteasome system through direct substrate targeting

Caspase-dependent regulation of the ubiquitin–proteasome system through direct substrate targeting

Quantitative Proteomics Analysis of the Effects of Ionizing Radiation in Wild Type and p53K317R Knock-in Mouse Thymocytes

Structure-Specific Recognition Protein 1 Facilitates Microtubule Growth and Bundling Required for Mitosis

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