PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger protein.
Ret finger protein (RFP) is a nuclear protein that is highly expressed in testis and in various tumor cell lines. RFP functions as a transcriptional repressor and associates with Enhancer of Polycomb 1 (EPC1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex. We show that RFP binds with PIAS (protein inhibitor of activated STAT) proteins, PIAS1, PIAS3, PIASxalpha and PIASy at their carboxyl-terminal region and is covalently modified by SUMO-1 (sumoylation). PIAS proteins enhance the sumoylation of RFP in a dose-dependent manner and induce the translocation of RFP into nuclear bodies reminiscent of the PML bodies. In addition, co-expression of PIAS proteins or SUMO-1 strengthened the transcriptional repressive activity of RFP. Finally, our immunohistochemical results show that RFP, SUMO-1 and PIASy localize in a characteristic nuclear structure juxtaposed with the inner nuclear membrane (XY body) of primary spermatocytes in mouse testis. These results demonstrate that the intracellular location and the transcriptional activity of RFP are modified by PIAS proteins which possess SUMO E3 ligase activities and suggest that they may play a co-operative role in spermatogenesis.
Matsuura
Tetsuo
T
Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Shimono
Yohei
Y
Kawai
Kumi
K
Murakami
Hideki
H
Urano
Takeshi
T
Niwa
Yasumasa
Y
Goto
Hidemi
H
Takahashi
Masahide
M
D000818:Animals; D002460:Cell Line; D002466:Cell Nucleolus / Q000737:chemistry / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT; D021381:Protein Transport / Q000502:physiology*; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D025842:SUMO-1 Protein / Q000378:metabolism*; D013090:Spermatocytes / Q000166:cytology / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000648:ultrastructure; D015533:Transcriptional Activation / Q000502:physiology*; D000070584:Tripartite Motif Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D025842:SUMO-1 Protein; C494211:Pias1 protein, mouse; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins