Premature Termination Codon: A Tunable Protein Translation Approach

Cheng, Xiyao; Zhou, Ting; Yang, Zixin; Zhou, Jingjing; Gao, Meng; Huang, Yongqi; Su, Zhengding

doi:10.2144/btn-2022-0046

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…4, the CTD domain of CCDC106 had no interaction with N-MdmX. Finally, we quantitively determined the binding affinity of p53 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] for the CTD domain with a Kd value of 0.32 µM (Supplementary Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

“…NCI-H1299, HCT116, MCF-7, A549, 293T and HepG2 cells were purchased from ATCC, and NCI-H1299 p53+ cell line was constructed in our group 22,23 . All kinds of cells were generally cultured in a 37 °C incubator with 5% CO2 according to ATCC protocols in RPMI-1640 medium (Gibco, USA) containing 10% fetal bovine serum (FBS, Gibco, USA), supplemented with 10% serum, penicillin and streptomycin.…”

Section: Cell Lines and Cell Culturesmentioning

confidence: 99%

“…Supplementary Fig. Quantitation of the interaction of CCDC106-CTD with p53 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] We quantitively determined the binding affinity of p53 15-29 for the CTD domain with a Kd value of 0.32 µM (Supplementary Fig. 5).…”

Section: Data Availabilitymentioning

confidence: 99%

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Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Zhou

Cheng

et al. 2023

Preprint

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The tumor suppressor p53 (p53) is regulated by murine double minute 2 (Mdm2) and its homologous MdmX in maintaining the p53 basal level. The overexpressed Mdm2/MdmX inhibit the cellular p53 activity, highly relevant to cancer occurrence. The coiled-coil domain-containing protein 106 (CCDC106) has been identified as a p53-interacting partner. However, its molecular mechanism is still elusive. Here we show that CCDC106 functions as a signaling regulator of the p53-Mdm2/MdmX axis mediated by cellular p53. We identified that CCDC106 directly interacts with the p53 transactivation domain by competing with Mdm2 and MdmX. The CCDC106 overexpression downregulates the cellular level of p53 and Mdm2/MdmX, and the decreased p53 reversibly downregulates the cellular level of CCDC106. Our work not only provides a molecular mechanism of CCDC106 regulating the cellular levels of p53 and Mdm2/MdmX, but also suggests that the CCDC106-p53 interaction as a novel target for cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Cell Lines and Cell Culturesmentioning

confidence: 99%

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Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Zhou

Cheng

et al. 2023

Preprint

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show abstract

“…NCI-H1299, HCT116, MCF-7, A549, 293T and HepG2 cells were purchased from ATCC, and the NCI-H1299 p53+ cell line was constructed in our group 22 , 23 . All kinds of cells were generally cultured in a 37 °C incubator with 5% CO 2 according to ATCC protocols in RPMI-1640 medium (Gibco, USA) containing 10% fetal bovine serum (FBS, Gibco, USA) supplemented with 10% serum, penicillin and streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signaling axis

Zhou,

Ke,

et al. 2023

Sci Rep

Self Cite

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The tumor suppressor p53 (p53) is regulated by murine double minute 2 (Mdm2) and its homologous MdmX in maintaining the basal level of p53. Overexpressed Mdm2/MdmX inhibits cellular p53 activity, which is highly relevant to cancer occurrence. Coiled-coil domain-containing protein 106 (CCDC106) has been identified as a p53-interacting partner. However, the molecular mechanism of the p53/Mdm2/MdmX/CCDC106 interactions is still elusive. Here, we show that CCDC106 functions as a signaling regulator of the p53-Mdm2/MdmX axis. We identified that CCDC106 directly interacts with the p53 transactivation domain by competing with Mdm2 and MdmX. CCDC106 overexpression downregulates the cellular level of p53 and Mdm2/MdmX, and decreased p53 reversibly downregulates the cellular level of CCDC106. Our work provides a molecular mechanism by which CCDC106 regulates the cellular levels of p53 and Mdm2/MdmX.

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“…Protein truncation, also referred to as premature protein termination brought on by a stop codon in a structural gene, is the elimination of a protein’s N- or C-terminal portion through proteolysis or structural gene manipulation ( 21 ). Protein truncating variants (PTVs) are genetic variants that alter transcription, leading to shorter proteins that may have implications on either protein loss or gain of function ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Unveiling the structure-emulsifying function relationship of truncated recombinant forms of the SA01-OmpA protein opens up a new vista in bioemulsifiers

Mohseni Sani,

Talaee,

Akbari

et al. 2024

Microbiol Spectr

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The emulsifying ability of SA01-OmpA (outer membrane protein A from Acinetobacter sp. SA01) was found to be constrained by challenges like low production efficiency and high costs associated with protein recovery from E. coli inclusion bodies, as described in our previous study. The present study sought to benefit from the advantages of the targeted truncating of SA01-OmpA protein, taking into account the reduced propensity of protein expression as inclusion bodies and cytotoxicity. Here, the structure and activity relationship of two truncated recombinant forms of SA01-OmpA protein was unraveled through a hybrid approach based on experimental data and computational methodologies, representing an innovative bioemulsifier with advantageous emulsifying activity. The recombinant truncated SA01-OmpA variants were cloned and heterologously expressed in E. coli host cells and subsequently purified. The results showed increased emulsifying activity of N-terminally truncated SA01-OmpA (NT-OmpA) compared to full-length SA01-OmpA. Molecular dynamics (MD) simulations analysis demonstrated a direct correlation between the C-terminally truncated SA01-OmpA (CT-OmpA) and its expression as inclusion bodies. Analysis of the structure-activity relationship of truncated variants of SA01-OmpA revealed that, compared to the full-length protein, deletion of the β-barrel portion from the N-terminal of SA01-OmpA increased the emulsifying activity of NT-OmpA while lowering its expression as inclusion bodies. Contrary to the full-length protein, the N-terminally truncated SA01-OmpA was not as cytotoxic, according to the MTT assay, FCM analysis, and AO/EB staining. The findings of this extensive study advance our knowledge of SA01-OmpA at the molecular level as well as the design and development of efficient bioemulsifiers. IMPORTANCE Previous research (Shahryari et al. 2021, mSystems 6: e01175-20) introduced and characterized the SA01-OmpA protein as a multifaceted protein with a variety of functions, including maintaining cellular homeostasis under oxidative stress conditions, biofilm formation, outer membrane vesicles (OMV) biogenesis, and beneficial emulsifying capacity. By truncating the SA01-OmpA protein, the current study presents a unique method for developing protein-type bioemulsifiers. The findings indicate that the N-terminally truncated SA01-OmpA (NT-OmpA) has the potential to fully replace full-length SA01-OmpA as a novel bioemulsifier with significant emulsifying activity. This study opens up a new frontier in bioemulsifiers, shedding light on a possible relationship between the structure and activity of SA01-OmpA truncated forms.

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Premature Termination Codon: A Tunable Protein Translation Approach

Cited by 5 publications

References 29 publications

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signaling axis

Unveiling the structure-emulsifying function relationship of truncated recombinant forms of the SA01-OmpA protein opens up a new vista in bioemulsifiers

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