The Identification of a Novel Gene, MAPO2, That Is Involved in the Induction of Apoptosis Triggered by O6-Methylguanine

Fujikane, Ryosuke; Sanada, Masayuki; Sekiguchi, Mutsuo; Hidaka, Masaaki

doi:10.1371/journal.pone.0044817

Cited by 11 publications

(9 citation statements)

References 26 publications

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“…Furthermore, the function of the ATP5J2-PTCD1 read-through transcript is completely unknown. Currently there exists minimal information regarding the function of STPG1 , the gene disrupted in family 4 examined here, besides a potential role in induced apoptosis pathways [42]. In this study, subsequent examination of PTCD1 , ATP5J2-PTCD1 and STPG1 coding exons on the alternative allele did not identify any point mutations in the affected members that could result in complete loss-of-function of these genes.…”

Section: Discussionmentioning

confidence: 67%

Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

et al. 2017

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Familial apparently balanced translocations (ABTs) segregating with discordant phenotypes are extremely challenging for interpretation and counseling due to the scarcity of publications and lack of routine techniques for quick investigation. Recently, next generation sequencing has emerged as an efficacious methodology for precise detection of translocation breakpoints. However, studies so far have mainly focused on de novo translocations. The present study focuses specifically on familial cases in order to shed some light to this diagnostic dilemma. Whole-genome mate-pair sequencing (WG-MPS) was applied to map the breakpoints in nine two-way ABT carriers from four families. Translocation breakpoints and patient-specific structural variants were validated by Sanger sequencing and quantitative Real Time PCR, respectively. Identical sequencing patterns and breakpoints were identified in affected and non-affected members carrying the same translocations. PTCD1, ATP5J2-PTCD1, CADPS2, and STPG1 were disrupted by the translocations in three families, rendering them initially as possible disease candidate genes. However, subsequent mutation screening and structural variant analysis did not reveal any pathogenic mutations or unique variants in the affected individuals that could explain the phenotypic differences between carriers of the same translocations. In conclusion, we suggest that NGS-based methods, such as WG-MPS, can be successfully used for detailed mapping of translocation breakpoints, which can also be used in routine clinical investigation of ABT cases. Unlike de novo translocations, no associations were determined here between familial two-way ABTs and the phenotype of the affected members, in which the presence of cryptic imbalances and complex chromosomal rearrangements has been excluded. Future whole-exome or whole-genome sequencing will potentially reveal unidentified mutations in the patients underlying the discordant phenotypes within each family. In addition, larger studies are needed to determine the exact percentage for phenotypic risk in families with ABTs.

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Section: Discussionmentioning

confidence: 67%

Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

et al. 2017

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“…However, a recent study demonstrated that TMZ-induced autophagy is pro-survival, and may block the eventual apoptosis in GBM cells (Knizhnik et al, 2013). Also, MAPO2 ( C1orf201 ) gene participates in the O6-methylguanine lesion-induced apoptosis (Fujikane et al, 2012). MAPO2 gene encodes a novel 37-kDa protein.…”

Section: Mechanisms Of Resistance To Temozolomide In Glioblastomasmentioning

confidence: 99%

Tumor Suppressor WWOX and p53 Alterations and Drug Resistance in Glioblastomas

Chiang¹,

Chou²,

Wang³

et al. 2013

Front. Oncol.

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Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide (TMZ) and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and postulate potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death.

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“…Sperm antigen like P36, a human sperm acrosomal antigen is involved in fertilization as well as male infertility [Auer et al 2004]. Motile sperm-domain containing protein-2 (MOSPD2), otherwise named O⁶-methylguanineinduced apoptosis 2 (MAPO2) is involved in the induction of apoptosis in the cells containing lesion due to O⁶-methylguanine [Fujikane et al 2012]. TPAP are expressed in round spermatids and play a major role in spermiogenesis [Kashiwabara et al 2000;Choi et al 2008].…”

Section: S Agalactiae Derived Non-self Peptidesmentioning

confidence: 99%

In silicoanalysis of candidate proteins sharing homology withStreptococcus agalactiaeproteins and their role in male infertility

Parida

Samanta

2016

Systems Biology in Reproductive Medicine

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Leukocytospermia is a physiologic condition defined as human semen with a leukocyte count of >1 x 10 6 cells/ml that is often correlated with male infertility. Moreover, bacteriospermia has been associated with leukocytospermia ultimately leading to male infertility. We have found that semen samples with >1 x 10 6 /ml leukocytes and/or bacteriospermia have oxidative predominance as evidenced by augmented protein carbonyl and lipid peroxidation status of the semen which is implicated in sperm dysfunction. It has been reported that Streptococcus agalactiae is present in bacteriospermic samples. Previous research has shown that human leukocyte antigen beta chain paralog (HLA-DRB) alleles interact best with the infected sperm cells rather than the non-infected cells. Little is known about the interaction of major histocompatibility complex (MHC) present on leukocytes with the sperm upon bacterial infection and how it induces an immunological response which we have addressed by epitope mapping. Therefore, we examined MHC class II derived bacterial peptides which might have human sperm-related functional aspects. Twenty-two S. agalactiae proteins were obtained from PUBMED protein database for our study. Protein sequences with more than two accession numbers were aligned using CLUSTAL Omega to check their conservation pattern. Each protein sequence was then analyzed for T-cell epitope prediction against HLA-DRB alleles using the immune epitope database (IEDB) analysis tool. Out of a plethora of peptides obtained from this analysis, peptides corresponding to proteins of interest such as DNA binding response regulator, hyaluronate lyase and laminin binding protein were screened against the human proteome using Blastp. Interestingly, we have found bacterial peptides sharing homology with human peptides deciphering some of the important sperm functions. Antibodies raised against these probable bacterial antigens of fertility will not only help us understand the mechanism of leukocytospermia/ bacteriospermia induced male factor infertility but also open new avenues for immunocontraception. Abbreviations: AA: amino acid; ASA: antisperm antibodies; GBS: group B streptococcus; HLA: human leukocyte antigen; HAS3: hyaluronan synthase 3: IEDB: immune epitope database; MAPO2: O 6 -methylguanine-induced apoptosis 2; MHC: major histocompatibility complex; ROS: reactive oxygen species; Rosbin1: round spermatid basic protein 1; S. agalactiae: Streptococcus agalactiae; SA: sperm antigen; SPATA17: spermatogenesis associated protein17; SPNR: spermatid perinuclear RNA binding protein; TEX15: testis-expressed sequence 15 protein; TOPAZ: testis-and ovaryspecific PAZ domain-containing protein; TPABP: testis-specific poly-A binding protein; TPAP: testis-specific poly(A) polymerase; WHO: World Health Organization ARTICLE HISTORY

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The Identification of a Novel Gene, MAPO2, That Is Involved in the Induction of Apoptosis Triggered by O6-Methylguanine

Cited by 11 publications

References 26 publications

Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

Tumor Suppressor WWOX and p53 Alterations and Drug Resistance in Glioblastomas

In silicoanalysis of candidate proteins sharing homology withStreptococcus agalactiaeproteins and their role in male infertility

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