摘要
Spermatogenesis is regulated by a complex network of posttranslation modifications.Sumoylation(a modification by small ubiquiti like modifiers,or SUMO proteins)was identified as an importa nt cellular event in d iff ere nt cell types.SUMO proteins are highly expressed in the testis,and their role during spermatogenesis has begun to be elucidated.Given the important role of sumoylation in the regulation of mitosis and cancer progress!on in other tissues,the aim of the current study was to identify the targets of SUMO in proliferating mouse spermatog onia and huma n semi noma tissues and to in itially exami ne the level of sumoylation in relation to the proliferative activity of the tissues.Using freshly purified spermatogonia and Cl8-4 spermatogonia cell line,mass spectrometry analysis identified several SUMO targets implicated into the proliferation of spermatogonia(such as heat shock protein 60[HSP60]and prohibitin).Tissue array and western blot approaches showed that SUMO expression is a prominent feature of human seminomas and that the proliferative activity of the tumor tissues was positively correlated with the level of SUMO expression.Down regulation of sumoylati on with si-RNA was not sufficie nt to sign ificantly affect the proliferation of C18-4 spermatogonia;however,SUMO overexpression in creased the proliferation rate of the cells.These data suggest that cells are more sensitive to an elevated level of SUMO,and that this situation may lead to an upregulated cellular proliferation and,possibly,cancer.Mass spectrometry analysis identified around a hundred SUMO targets in seminoma samples.Notably,many of the identified proteins(such as proliferating cell nuclear antigen[PCNA],DNA topoisomerase 2-alpha[Top2A],prohibitin,14-3-3 protein,and others)were implicated in oncogenic transformation and cancer progression.
