Scanning of novel cancer/testis proteins by human testis proteomic analysis

Liu, Mingxi; Hu, Zhibin; Lin, Qingsong; Wang, Jing; Zhou, Tao; Guo, Yueshuai; Zeng, Yan; Zheng, Bo; Wu, Yibo; Zhang, Pan; Chen, Xin; Tu, Wenjiao; Zhang, Ting; Zhou, Quan; Jiang, Min; Guo, Xuejiang; Zhou, Zuomin; Sha, Jiahao

doi:10.1002/pmic.201200489

Cited by 57 publications

(53 citation statements)

References 72 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that chemotherapy negatively affects spermatogenesis, either transiently or permanently [30,31]. Interestingly, it is also well established that there are similarities between cancer cells and those in the germ cell differentiation pathway [32][33][34]. One of these features is telomere maintenance for immortalization of both germ cells and cancer cells.…”

Section: Discussionmentioning

confidence: 96%

Effects of Four Chemotherapeutic Agents, Bleomycin, Etoposide, Cisplatin, and Cyclophosphamide, on DNA Damage and Telomeres in a Mouse Spermatogonial Cell Line1

Liu

Hales

Robaire

2014

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Treatment with chemotherapeutics agents may induce persistent DNA damage in male germ cells with the possibility of long-term consequences on fertility and progeny outcome. Telomeres, specialized structures at the physical ends of chromosomes, play an important role in the maintenance of genetic stability and in the response of somatic cells to anticancer drugs. Our objective was to test the hypothesis that exposure to bleomycin, etoposide, or cisplatin (the drugs used to treat testicular cancer) or cyclophosphamide (an anticancer agent and immunosuppressant) targets telomeres in the male germ line. C18-4 spermatogonial cells were exposed to bleomycin, etoposide, cisplatin, or 4-hydroperoxycyclophosphamide (4OOH-CPA, a preactivated analog of cyclophosphamide). All four anticancer drugs induced a significant increase in DNA damage in C18-4 cells, as assessed by gamma-H2AX immunofluorescence. Interestingly, the gamma-H2AX signal was localized to telomeres after treatment with bleomycin, cisplatin, and 4OOH-CPA, but not etoposide. Mean telomere lengths, the intensity of the telomere fluorescence in situ hybridization signal, telomerase activity, and the expression of the telomerase enzyme mRNA components, Tert and Terc, were reduced by exposure to cisplatin and 4OOH-CPA, but not by bleomycin or etoposide. Thus, although all four anticancer drugs induced DNA damage in this spermatogonial cell line, telomeres were not specifically affected by etoposide and only the two alkylating agents, cisplatin and 4OOH-CPA, induced telomere dysfunction. This telomere dysfunction may contribute to infertility and developmental defects in the offspring.

show abstract

Section: Discussionmentioning

confidence: 96%

Effects of Four Chemotherapeutic Agents, Bleomycin, Etoposide, Cisplatin, and Cyclophosphamide, on DNA Damage and Telomeres in a Mouse Spermatogonial Cell Line1

Liu

Hales

Robaire

2014

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

show abstract

“…Each 100-mg protein sample was reduced with dithiothreitol, alkylated with iodoacetamide, and digested with trypsin (13,14). Tandem mass tag (TMT) labeling (Pierce) was performed according to the manufacturer's protocol with minor modifications.…”

Section: Tandem Mass Tag Labeling Scx Fractionation and Ms Analysismentioning

confidence: 99%

Long-term effects of repeated superovulation on ovarian structure and function in rhesus monkeys

Dong

Guo

Cao

et al. 2014

Fertility and Sterility

Self Cite

View full text Add to dashboard Cite

“…Sperms are produced in the male testis at the speed of ϳ1000 sperm per heart beat (1), which indicate that spermatogenesis is an extremely dynamic process in the testis. The protein expression levels during spermatogenesis have been well studied by high-throughput proteomic studies, and over 7000 proteins have been identified in the mammalian testis (2)(3)(4). However, the dynamic regulatory events that orchestrate this complex process have yet to be elucidated.…”

mentioning

confidence: 99%

Systematic Analysis of the Phosphoproteome and Kinase-substrate Networks in the Mouse Testis

Lin

Liu

Wang

et al. 2014

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

Spermatogenesis is a complex process closely associated with the phosphorylation-orchestrated cell cycle. Elucidating the phosphorylation-based regulations should advance our understanding of the underlying molecular mechanisms. Here we present an integrative study of phosphorylation events in the testis. Large-scale phosphoproteome profiling in the adult mouse testis identified 17,829 phosphorylation sites in 3955 phosphoproteins. Although only approximately half of the phosphorylation sites enriched by IMAC were also captured by TiO 2 , both the phosphoprotein data sets identified by the two methods significantly enriched the functional annotation of spermatogenesis. Thus, the phosphoproteome profiled in this study is a highly useful snapshot of the phosphorylation events in spermatogenesis. To further understand phosphoregulation in the testis, the site-specific kinasesubstrate relations were computationally predicted for reconstructing kinase-substrate phosphorylation networks. A core sub-kinase-substrate phosphorylation networks among the spermatogenesis-related proteins was retrieved and analyzed to explore the phosphoregulation during spermatogenesis. Moreover, network-based analyses demonstrated that a number of protein kinases such as MAPKs, CDK2, and CDC2 with statistically more sitespecific kinase-substrate relations might have significantly higher activities and play an essential role in spermatogenesis, and the predictions were consistent with previous studies on the regulatory roles of these kinases. In particular, the analyses proposed that the activities of POLO-like kinases (PLKs) might be dramatically higher, while the prediction was experimentally validated by detecting and comparing the phosphorylation levels of pT210, an indicator of PLK1 activation, in testis and other tissues. Further experiments showed that the inhibition of POLO-like kinases decreases cell proliferation by inducing G2/M cell cycle arrest. Taken together, this systematic study provides a global landscape of phosphoregulation in the testis, and should prove to be of value in future studies of spermatogenesis. Molecular & Cellular Proteomics 13:

show abstract

Scanning of novel cancer/testis proteins by human testis proteomic analysis

Cited by 57 publications

References 72 publications

Effects of Four Chemotherapeutic Agents, Bleomycin, Etoposide, Cisplatin, and Cyclophosphamide, on DNA Damage and Telomeres in a Mouse Spermatogonial Cell Line1

Effects of Four Chemotherapeutic Agents, Bleomycin, Etoposide, Cisplatin, and Cyclophosphamide, on DNA Damage and Telomeres in a Mouse Spermatogonial Cell Line1

Long-term effects of repeated superovulation on ovarian structure and function in rhesus monkeys

Systematic Analysis of the Phosphoproteome and Kinase-substrate Networks in the Mouse Testis

Contact Info

Product

Resources

About