RNF4 is a growth inhibitor expressed in germ cells but not in human testicular tumors.
The RING-finger protein RNF4 modulates both steroid-receptor-dependent and basal transcription and interacts with a variety of nuclear proteins involved in cell growth control. RNF4 is expressed at very high levels in testis and at much lower levels in several other tissues. We show that in germ cells RNF4 expression is strongly modulated during progression of spermatogonia to spermatids, with a peak in spermatocytes. Analysis of human testicular germ cell tumors shows that RNF4 is not expressed in all tumors analyzed including seminomas, the highly malignant embryonal carcinomas, yolk sac, and mixed germ cell tumors. We also show that the ectopically expressed RNF4 gene inhibits cell proliferation of both somatic and germ cell tumor-derived cells. Mutation of critical cysteine residues in the RING finger domain abolished the RNF4 growth inhibition activity. Our results suggest that the lack of RNF4 expression may play a role in the progression of testicular tumors.
Pero
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Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano Centro di Endocrinologia ed Oncologia Sperimentale del CNR G. Salvatore, Università degli Studi di Napoli Federico II, Napoli, Italy.
Lembo
F
F
Di Vizio
D
D
Boccia
A
A
Chieffi
P
P
Fedele
M
M
Pierantoni
G M
GM
Rossi
P
P
Iuliano
R
R
Santoro
M
M
Viglietto
G
G
Bruni
C B
CB
Fusco
A
A
Chiariotti
L
L
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins; D012016:Reference Values; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013736:Testicular Neoplasms / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D009687:Nuclear Proteins; C114070:RNF4 protein, human; D014157:Transcription Factors; C486410:Rnf4 protein, mouse; D044767:Ubiquitin-Protein Ligases