Microtubule-associated protein (MAP) 4 interacts with microtubules in an intrinsically disordered manner

Hashi, Yurika; Kawai, Gota; Kotani, Susumu

doi:10.1080/09168451.2014.940836

Cited by 5 publications

(3 citation statements)

References 36 publications

(30 reference statements)

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“…Hashi et al created a minimal active fragment of MAP4 in order to make this protein sizecompatible with NMR, and found that MAP4 is an IDP that binds to a microtubule in a multivalent manner, using its multiple binding sites. 26 This observation contradicts previous data, which indicated that multiple binding sites acted simultaneously on multiple microtubules.…”

Section: Studies On Structural Properties Of Idps and Idprscontrasting

confidence: 71%

Quarterly intrinsic disorder digest (January-February-March, 2014)

DeForte

Reddy

Uversky

2016

Intrinsically Disordered Proteins

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This is the 5 th issue of the Digested Disorder series that represents a reader's digest of the scientific literature on intrinsically disordered proteins. We continue to use only 2 criteria for inclusion of a paper to this digest: The publication date (a paper should be published within the covered time frame) and the topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the first quarter of 2014; i.e., during the period of January, February, and March of 2014. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included papers a short description is given on its major findings. The goal of this series is to provide an unbiased and condensed survey of the literature on intrinsically disordered proteins on a quarterly basis. As in the previous issues, no special filtering was used except to verify the print date, and exclude those papers not related to the topic. The digest article is structured hierarchically and papers are grouped in several sections: (1) structures of intrinsically disordered proteins (IDPs); (2) functions of IDPs; (3) methods for the IDP analysis; (4) proteomics of IDPs; (5) IDPs and diseases; and (6) IDPs/IDPRs as drugs or drug targets. One should keep in mind that the unambiguous classification of many papers is challenged by the intertwining of the topics they cover.In the 5 th digest of this series, we cover papers published in January, February, and March of 2014. We used the following search term in PubMed: (intrinsically OR natively OR naturally OR inherently) AND (disordered OR unfolded OR unstructured OR denatured) AND (protein OR region OR peptide OR domain) AND ("2014/01" [PPDAT]: "2014/ 03"[PPDAT]), which returned 103 hits. After filtering hits not relevant to the topic, we have covered 94 articles here. Figure 1 represents a word cloud, which shows the most represented words from all the abstracts of papers included in this issue.We also introduce below a new rubric "Spotlight" that specifically emphasize some of the most interesting and important developments in the field of intrinsically disordered proteins during the covered quarter. Spotlight: IDP databases and the rise of the ensemble viewDatabases of experimentally verified IDPs are critical for the development of tools that predict intrinsic disorder, and provide an important data set for the study of IDP functions, motifs and structural behavior. One of the first databases to provide experimental evidence of intrinsic disorder was oddly enough, the Protein Data Bank, where regions of missing electron density in x-ray crystal structures provide an indication of possible disorder. The major databases for IDPs are Disprot 5 and the recently updated IDEAL 6 and the mostly predictor based databases d2p2 7 and MobiDB.8 CONTACT Vladimir N. Uversky

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Section: Studies On Structural Properties Of Idps and Idprscontrasting

confidence: 71%

Quarterly intrinsic disorder digest (January-February-March, 2014)

DeForte

Reddy

Uversky

2016

Intrinsically Disordered Proteins

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“…It has been reported that IDRs in MAPs, for example, tau proteins MAP1, MAP2, and MAP4 are involved in multiple molecular interactions and important for normal physiology; as such, variants in IDRs of these MAPs are linked to diseases (30)(31)(32)(33). In the other report, Leu S, et al showed the alternation at IDR region in phosphoglycerate mutase 1 (PGAM1) molecule led to conformational change and influenced the cofactor binding at the catalytic site (34).…”

Section: Discussionmentioning

confidence: 99%

A variant in the RP1L1 gene in a family with occult macular dystrophy in a predicted intrinsically disordered region

Hiraoka

Ishikawa

Matsuzawa³

et al. 2020

Ophthalmic Genetics

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Significance: The responsible genetic variants for occult macular dystrophy (OMD) were found at the predicted intrinsically disordered region (IDR) of the RP1L1 gene. Purpose: We examined the phenotypes and genotypes of family members from OMD. In addition, the genetic characteristics of the RP1L1 gene in OMD were investigated. Methods: Whole-exome sequencing was applied on two affected family members, and Sanger sequencing was performed on three members. The structural property of RP1L1 and pathogenic variants was analyzed using predictor of natural disordered regions (PONDR). Results: Two affected members showed moderate visual impairment and relative central scotoma. The spectral domain optical coherence tomography (SD-OCT) images showed an absence of the interdigitation zone (IZ) and ellipsoid zone (EZ) in one case, and an obscure EZ line in the other case. A RP1L1 variant (c.3593 C > T, p.Ser1198Phe) was identified in two affected members but not in the unaffected member. The PONDR analysis showed that the region from p.1189 to p.1248 could be predicted to be an IDR in the RP1L1 molecule. And the p. Ser1198Phe variant showed significant reduction of PONDR score. Conclusions: Although, the major pathogenic variant of OMD is p.Arg45Trp, multiple reports indicate that the region between p.1194 and p.1201 is another hot spot of OMD. The PONDR analysis predicted that the RP1L1 molecule is one of the intrinsically disordered proteins. It is speculated that the region around p.1200 is essential for the normal function of the RP1L1 molecule, and the missense variants of that area cause the development of OMD.

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“…Perturbations in microtubule dynamics are closely related to cancer cell behaviour (Győrffy et al 2014 ). Microtubules reorganize to promote cancer-related activities, such as mitosis and migration, to promote tumour growth and metastasis, respectively (Győrffy et al 2014 ; Hashi et al 2014 ). MAP4 is the major MAP protein expressed in nonneuronal mammalian cells and is able to regulate microtubule assembly and stability in vitro and in vivo (Hu et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial–mesenchymal transition in lung adenocarcinoma

Xia,

Ge,

et al. 2024

J Cancer Res Clin Oncol

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Purpose To explore the effect of microtubule-associated protein 4 (MAP4) on lung adenocarcinoma cells in vitro and evaluate its prognostic value. Radioresistance, indicated by reduced efficiency of radiotherapy, is a key factor in treatment failure in lung adenocarcinoma (LADC). This study aims to explore the primary mechanism underlying the relationship between MAP4 and radiation resistance in lung adenocarcinoma. Methods We analysed the expression of MAP4 in lung adenocarcinoma by real-time quantitative polymerase chain reaction (RT‒qPCR), immunohistochemistry (IHC) and bioinformatics online databases, evaluated the prognostic value of MAP4 in lung adenocarcinoma and studied its relationship with clinicopathological parameters. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis identified independent prognostic factors associated with lung adenocarcinoma that were used to construct a nomogram, internal validation was performed. We then evaluated the accuracy and clinical validity of the model using a receiver operating characteristic (ROC) curve, time-dependent C-index analysis, a calibration curve, and decision curve analysis (DCA). Scratch assays and transwell assays were used to explore the effect of MAP4 on the migration and invasion of lung adenocarcinoma cells. Bioinformatics analysis, RT‒qPCR, Cell Counting Kit-8 (CCK-8) assays and Western blot experiments were used to study the relationship between MAP4, epithelial–mesenchymal transition (EMT) and radiation resistance in lung adenocarcinoma. Results MAP4 expression in lung adenocarcinoma tissues was significantly higher than that in adjacent normal lung tissues. High expression of MAP4 is associated with poorer overall survival (OS) in patients with lung adenocarcinoma. Univariate Cox regression analysis showed that pT stage, pN stage, TNM stage and MAP4 expression level were significantly associated with poorer OS in LADC patients. Multivariate Cox regression analysis and LASSO regression analysis showed that only the pT stage and MAP4 expression level were associated with LADC prognosis. The nomogram constructed based on the pT stage and MAP4 expression showed good predictive accuracy. ROC curves, corrected C-index values, calibration curves, and DCA results showed that the nomogram performed well in both the training and validation cohorts and had strong clinical applicability. The results of in vitro experiments showed that the downregulation of MAP4 significantly affected the migration and invasion of lung adenocarcinoma cells. MAP4 was strongly correlated with EMT-related markers. Further studies suggested that the downregulation of MAP4 can affect the viability of lung adenocarcinoma cells after irradiation and participate in the radiation resistance of lung adenocarcinoma cells by affecting EMT. Conclusion MAP4 is highly expressed in lung adenocarcinoma; it may affect prognosis by promoting the migration and invasion of cancer cells. We developed a nomogram including clinical factors and MAP4 expression that can be used for prognosis prediction in patients with lung adenocarcinoma. MAP4 participates in radiation resistance in lung adenocarcinoma by regulating the radiation-induced EMT process. MAP4 may serve as a biomarker for lung adenocarcinoma prognosis evaluation and as a new target for improving radiosensitivity.

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Microtubule-associated protein (MAP) 4 interacts with microtubules in an intrinsically disordered manner

Cited by 5 publications

References 36 publications

Quarterly intrinsic disorder digest (January-February-March, 2014)

Quarterly intrinsic disorder digest (January-February-March, 2014)

A variant in the RP1L1 gene in a family with occult macular dystrophy in a predicted intrinsically disordered region

MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial–mesenchymal transition in lung adenocarcinoma

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