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Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue

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Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue. / Huber, René; Augsten, Sandra; Kirsten, Holger; Zell, Roland; Stelzner, Axel; Thude, Hansjörg; Eidner, Thorsten; Stuhlmüller, Bruno; Ahnert, Peter; Kinne, Raimund W.

in: LIFE-BASEL, Jahrgang 11, Nr. 1, 23.12.2020.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Huber, R, Augsten, S, Kirsten, H, Zell, R, Stelzner, A, Thude, H, Eidner, T, Stuhlmüller, B, Ahnert, P & Kinne, RW 2020, 'Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue', LIFE-BASEL, Jg. 11, Nr. 1. https://doi.org/10.3390/life11010005

APA

Huber, R., Augsten, S., Kirsten, H., Zell, R., Stelzner, A., Thude, H., Eidner, T., Stuhlmüller, B., Ahnert, P., & Kinne, R. W. (2020). Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue. LIFE-BASEL, 11(1). https://doi.org/10.3390/life11010005

Vancouver

Huber R, Augsten S, Kirsten H, Zell R, Stelzner A, Thude H et al. Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue. LIFE-BASEL. 2020 Dez 23;11(1). https://doi.org/10.3390/life11010005

Bibtex

@article{b4595d6732b4400e9826cc8852362855,
title = "Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue",
abstract = "In rheumatoid arthritis (RA), the expression of many pro-destructive/pro-inflammatory proteins depends on the transcription factor AP-1. Therefore, our aim was to analyze the presence and functional relevance of mutations in the coding regions of the AP-1 subunits of the fos and jun family in peripheral blood (PB) and synovial membranes (SM) of RA and osteoarthritis patients (OA, disease control), as well as normal controls (NC). Using the non-isotopic RNAse cleavage assay, one known polymorphism (T252C: silent; rs1046117; present in RA, OA, and NC) and three novel germline mutations of the cfos gene were detected: (i) C361G/A367G: Gln121Glu/Ile123Val, denoted as {"}fos121/123{"}; present only in one OA sample; (ii) G374A: Arg125Lys, {"}fos125{"}; and (iii) C217A/G374A: Leu73Met/Arg125Lys, {"}fos73/125{"}, the latter two exclusively present in RA. In addition, three novel somatic cjun mutations (604-606ΔCAG: ΔGln202, {"}jun202{"}; C706T: Pro236Ser, {"}jun236{"}; G750A: silent) were found exclusively in the RA SM. Tansgenic expression of fos125 and fos73/125 mutants in NIH-3T3 cells induced an activation of reporter constructs containing either the MMP-1 (matrix metalloproteinase) promoter (3- and 4-fold, respectively) or a pentameric AP-1 site (approximately 5-fold). Combined expression of these two cfos mutants with cjun wildtype or mutants (jun202, jun236) further enhanced reporter expression of the pentameric AP-1 construct. Finally, genotyping for the novel functionally relevant germline mutations in 298 RA, 288 OA, and 484 NC samples revealed no association with RA. Thus, functional cfos/cjun mutants may contribute to local joint inflammation/destruction in selected patients with RA by altering the transactivation capacity of AP-1 complexes.",
author = "Ren{\'e} Huber and Sandra Augsten and Holger Kirsten and Roland Zell and Axel Stelzner and Hansj{\"o}rg Thude and Thorsten Eidner and Bruno Stuhlm{\"u}ller and Peter Ahnert and Kinne, {Raimund W}",
year = "2020",
month = dec,
day = "23",
doi = "10.3390/life11010005",
language = "English",
volume = "11",
journal = "LIFE-BASEL",
issn = "2075-1729",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "1",

}

RIS

TY - JOUR

T1 - Identification of New, Functionally Relevant Mutations in the Coding Regions of the Human Fos and Jun Proto-Oncogenes in Rheumatoid Arthritis Synovial Tissue

AU - Huber, René

AU - Augsten, Sandra

AU - Kirsten, Holger

AU - Zell, Roland

AU - Stelzner, Axel

AU - Thude, Hansjörg

AU - Eidner, Thorsten

AU - Stuhlmüller, Bruno

AU - Ahnert, Peter

AU - Kinne, Raimund W

PY - 2020/12/23

Y1 - 2020/12/23

N2 - In rheumatoid arthritis (RA), the expression of many pro-destructive/pro-inflammatory proteins depends on the transcription factor AP-1. Therefore, our aim was to analyze the presence and functional relevance of mutations in the coding regions of the AP-1 subunits of the fos and jun family in peripheral blood (PB) and synovial membranes (SM) of RA and osteoarthritis patients (OA, disease control), as well as normal controls (NC). Using the non-isotopic RNAse cleavage assay, one known polymorphism (T252C: silent; rs1046117; present in RA, OA, and NC) and three novel germline mutations of the cfos gene were detected: (i) C361G/A367G: Gln121Glu/Ile123Val, denoted as "fos121/123"; present only in one OA sample; (ii) G374A: Arg125Lys, "fos125"; and (iii) C217A/G374A: Leu73Met/Arg125Lys, "fos73/125", the latter two exclusively present in RA. In addition, three novel somatic cjun mutations (604-606ΔCAG: ΔGln202, "jun202"; C706T: Pro236Ser, "jun236"; G750A: silent) were found exclusively in the RA SM. Tansgenic expression of fos125 and fos73/125 mutants in NIH-3T3 cells induced an activation of reporter constructs containing either the MMP-1 (matrix metalloproteinase) promoter (3- and 4-fold, respectively) or a pentameric AP-1 site (approximately 5-fold). Combined expression of these two cfos mutants with cjun wildtype or mutants (jun202, jun236) further enhanced reporter expression of the pentameric AP-1 construct. Finally, genotyping for the novel functionally relevant germline mutations in 298 RA, 288 OA, and 484 NC samples revealed no association with RA. Thus, functional cfos/cjun mutants may contribute to local joint inflammation/destruction in selected patients with RA by altering the transactivation capacity of AP-1 complexes.

AB - In rheumatoid arthritis (RA), the expression of many pro-destructive/pro-inflammatory proteins depends on the transcription factor AP-1. Therefore, our aim was to analyze the presence and functional relevance of mutations in the coding regions of the AP-1 subunits of the fos and jun family in peripheral blood (PB) and synovial membranes (SM) of RA and osteoarthritis patients (OA, disease control), as well as normal controls (NC). Using the non-isotopic RNAse cleavage assay, one known polymorphism (T252C: silent; rs1046117; present in RA, OA, and NC) and three novel germline mutations of the cfos gene were detected: (i) C361G/A367G: Gln121Glu/Ile123Val, denoted as "fos121/123"; present only in one OA sample; (ii) G374A: Arg125Lys, "fos125"; and (iii) C217A/G374A: Leu73Met/Arg125Lys, "fos73/125", the latter two exclusively present in RA. In addition, three novel somatic cjun mutations (604-606ΔCAG: ΔGln202, "jun202"; C706T: Pro236Ser, "jun236"; G750A: silent) were found exclusively in the RA SM. Tansgenic expression of fos125 and fos73/125 mutants in NIH-3T3 cells induced an activation of reporter constructs containing either the MMP-1 (matrix metalloproteinase) promoter (3- and 4-fold, respectively) or a pentameric AP-1 site (approximately 5-fold). Combined expression of these two cfos mutants with cjun wildtype or mutants (jun202, jun236) further enhanced reporter expression of the pentameric AP-1 construct. Finally, genotyping for the novel functionally relevant germline mutations in 298 RA, 288 OA, and 484 NC samples revealed no association with RA. Thus, functional cfos/cjun mutants may contribute to local joint inflammation/destruction in selected patients with RA by altering the transactivation capacity of AP-1 complexes.

U2 - 10.3390/life11010005

DO - 10.3390/life11010005

M3 - SCORING: Journal article

C2 - 33374881

VL - 11

JO - LIFE-BASEL

JF - LIFE-BASEL

SN - 2075-1729

IS - 1

ER -