Proteome balance in ciliopathies: the OFD1 protein example

Morleo, Manuela; Pezzella, Nunziana; Franco, Brunella

doi:10.1016/j.molmed.2022.11.007

Cited by 6 publications

(4 citation statements)

References 114 publications

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“…Also among the DIFFRAC hits were many proteins with known roles in protein synthesis, in particular, many subunits of the tRNA multi-synthetase complex, translation elongation factors and ribosomal proteins (Fig S2), These data suggest the possibility that IFT-A, like other ciliopathy proteins (Morleo et al ., 2022), may play a broader role in proteome regulation. These results encourage further study to determine whether IFT-A contributes to localized translation that has been proposed to occur at either basal bodies (Lerit, 2022) or within cilia (Hao et al ., 2021).…”

Section: Resultsmentioning

confidence: 92%

Label-free proteomic comparison reveals ciliary and non-ciliary phenotypes of IFT-A mutants

Leggere

Hibbard

Papoulas

et al. 2023

Preprint

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DIFFRAC is a powerful method for systematically comparing proteome content and organization between samples in a high-throughput manner. By subjecting control and experimental protein extracts to native chromatography and quantifying the contents of each fraction using mass spectrometry, it enables the quantitative detection of alterations to protein complexes and abundances. Here, we applied DIFFRAC to investigate the consequences of genetic loss of Ift122, a subunit of the intraflagellar transport-A (IFT-A) protein complex that plays a vital role in the formation and function of cilia and flagella, on the proteome of Tetrahymena thermophila. A single DIFFRAC experiment was sufficient to detect changes in protein behavior that mirrored known effects of IFT-A loss and revealed new biology. We uncovered several novel IFT-A- regulated proteins, which we validated through live imaging in Xenopus multiciliated cells, shedding new light on both the ciliary and non-ciliary functions of IFT-A. Our findings underscore the robustness of DIFFRAC for revealing proteomic changes in response to genetic or biochemical perturbation.

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Section: Resultsmentioning

confidence: 92%

Label-free proteomic comparison reveals ciliary and non-ciliary phenotypes of IFT-A mutants

Leggere

Hibbard

Papoulas

et al. 2023

Preprint

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“…In addition to its role in early embryonic development, OFD1 plays an important role in cellular processes such as autophagy ( 49 – 51 ). In particular, OFD1 is the first example of a ciliopathy protein that controls protein expression and autophagy/proteasome degradation, providing directions for the treatment of various diseases ( 52 ). USPL1 (Ubiquitin-Specific Peptidase-Like 1) is a gene that encodes a protein.…”

Section: Discussionmentioning

confidence: 99%

Identification of cuproptosis-related gene clusters and immune cell infiltration in major burns based on machine learning models and experimental validation

Wang,

Xiong,

Hong

et al. 2024

Front. Immunol.

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IntroductionBurns are a global public health problem. Major burns can stimulate the body to enter a stress state, thereby increasing the risk of infection and adversely affecting the patient’s prognosis. Recently, it has been discovered that cuproptosis, a form of cell death, is associated with various diseases. Our research aims to explore the molecular clusters associated with cuproptosis in major burns and construct predictive models.MethodsWe analyzed the expression and immune infiltration characteristics of cuproptosis-related factors in major burn based on the GSE37069 dataset. Using 553 samples from major burn patients, we explored the molecular clusters based on cuproptosis-related genes and their associated immune cell infiltrates. The WGCNA was utilized to identify cluster-specific genes. Subsequently, the performance of different machine learning models was compared to select the optimal model. The effectiveness of the predictive model was validated using Nomogram, calibration curves, decision curves, and an external dataset. Finally, five core genes related to cuproptosis and major burn have been was validated using RT-qPCR.ResultsIn both major burn and normal samples, we determined the cuproptosis-related genes associated with major burns through WGCNA analysis. Through immune infiltrate profiling analysis, we found significant immune differences between different clusters. When K=2, the clustering number is the most stable. GSVA analysis shows that specific genes in cluster 2 are closely associated with various functions. After identifying the cross-core genes, machine learning models indicate that generalized linear models have better accuracy. Ultimately, a generalized linear model for five highly correlated genes was constructed, and validation with an external dataset showed an AUC of 0.982. The accuracy of the model was further verified through calibration curves, decision curves, and modal graphs. Further analysis of clinical relevance revealed that these correlated genes were closely related to time of injury.ConclusionThis study has revealed the intricate relationship between cuproptosis and major burns. Research has identified 15 cuproptosis-related genes that are associated with major burn. Through a machine learning model, five core genes related to cuproptosis and major burn have been selected and validated.

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“…自噬在初级纤毛发生和中间体残体的降解中均发挥关键作用。OFD1位于中心体上，是细胞器发生选择性自噬降解的关键蛋白。通过免疫荧光技术发现，OFD1在初级纤毛降解时共定位于初级纤毛，说明自噬是初级纤毛降解的关键步骤［ 50 ］。同时，抑制细胞自噬可以恢复甲状腺嗜酸性肿瘤细胞初级纤毛的发生，并促进IFT88和ARL13B的积累。在干细胞的研究中表明，抑制细胞自噬可以使初级纤毛发生更快［ 51 ］。在肿瘤细胞中聚集积累的多余中间体残体通过F-肌动蛋白机制吞噬入细胞进行降解，使中间体残体与中心体的结合不再受阻［ 27 ］，从而促进初级纤毛的生成，进而使肿瘤的细胞周期趋于正常。并且初级纤毛的形成可调节肿瘤细胞自噬通量的变化，进而影响残余体降解，促进肿瘤细胞增殖。在肿瘤发生早期，肿瘤细胞更倾向于富集中间体残体，但由于肿瘤细胞不能通过自噬降解富集的中间体残体，残余的中间体残体不能与中心体正常结合从而导致初级纤毛数显著减少，表现出抑癌作用［ 50 - 51 ］；在肿瘤进展晚期，自噬水平上调导致初级纤毛数增加并且促进肿瘤细胞的淋巴结转移［ 52 ］。…”

Section: 初级纤毛和中间体残体在肿瘤中的作用unclassified

Midbody remnant regulates the formation of primary cilia and its relation with tumorigenesis and tumor progression

LI,

ZHAO

et al. 2024

J Zhejiang Univ (Med Sci)

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最新研究表明，初级纤毛细胞外发生途径与一种特殊细胞器—中间体残体相关。中间体残体是细胞有丝分裂末期中间体脱落形成的点状细胞器，中间体残体形成后在细胞表面移动，当与中心体在细胞表面靠近后，调节中心体在其母中心粒的顶端形成初级纤毛。初级纤毛可作为抑制肿瘤发生的细胞器，并在多种肿瘤中丢失，研究发现中间体残体在肿瘤细胞中聚集影响初级纤毛的发生。更重要的是，中间体残体和初级纤毛在肿瘤细胞中均通过自噬途径降解，中间体残体还可以将肿瘤信号通路因子传递给初级纤毛进而影响肿瘤细胞的发生发展。本文综述了中间体残体和初级纤毛的基本结构及形成过程，详细阐述了中间体残体调控初级纤毛发生的具体机制，探讨及展望了中间体残体调控初级纤毛形成在肿瘤发生发展和靶向治疗中的作用及研究趋势。

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Proteome balance in ciliopathies: the OFD1 protein example

Cited by 6 publications

References 114 publications

Label-free proteomic comparison reveals ciliary and non-ciliary phenotypes of IFT-A mutants

Label-free proteomic comparison reveals ciliary and non-ciliary phenotypes of IFT-A mutants

Identification of cuproptosis-related gene clusters and immune cell infiltration in major burns based on machine learning models and experimental validation

Midbody remnant regulates the formation of primary cilia and its relation with tumorigenesis and tumor progression

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