Modification of the erythroid transcription factor GATA-1 by SUMO-1.
The activity of transcription factors is tightly modulated by posttranslational modifications affecting stability, localization, and protein-protein interactions. Conjugation to SUMO is a reversible posttranslational modification that has been shown to regulate important transcription factors involved in cell proliferation, differentiation, and tumor suppression. Here, we demonstrate that the erythroid transcription factor GATA-1 is sumoylated in vitro and in vivo and map the single lysine residue involved in SUMO-1 attachment. We show that the nuclear RING finger protein PIASy promotes sumoylation of GATA-1 and dramatically represses its transcriptional activity. We present evidence that a nonsumoylatable GATA-1 mutant is indistinguishable from the WT protein in its ability to transactivate a reporter gene in mammalian cells and in its ability to trigger endogenous globin expression in Xenopus explants. These observations open interesting questions about the biological role of this posttranslational modification of GATA-1.
Collavin
Licio
L
Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy.
Gostissa
Monica
M
Avolio
Fabio
F
Secco
Paola
P
Ronchi
Antonella
A
Santoro
Claudio
C
Del Sal
Giannino
G
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D020014:K562 Cells; D008239:Lysine / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D050828:Protein Inhibitors of Activated STAT; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; D008239:Lysine