SUMO-1 protease-1 regulates gene transcription through PML.
During a screen to identify c-Jun activators, we isolated a cysteine protease, SuPr-1, that induced c-Jun-dependent transcription independently of c-Jun phosphorylation. SuPr-1 is a member of a new family of proteases that hydrolyze the ubiquitin-like modifier, SUMO-1. SuPr-1 hydrolyzed SUMO-1-modified forms of the promyelocytic leukemia gene product, PML, and altered the subcellular distribution of PML in nuclear PODs (PML oncogenic domains). SuPr-1 also altered the distribution of other nuclear POD-associated proteins, such as CBP and Daxx, that act as transcriptional regulators. SuPr-1 action on transcription was enhanced by PML, and SuPr-1 failed to activate transcription in PML-deficient fibroblasts. Our studies establish an important role for SUMO proteases in transcription.
Best
Jennifer L
JL
Division of Hematology/Oncology, Children's Hospital, Department of Medicine, Boston, MA 02115, USA.
Ganiatsas
Soula
S
Agarwal
Sadhana
S
Changou
Austin
A
Salomoni
Paolo
P
Shirihai
Orian
O
Meluh
Pamela B
PB
Pandolfi
Pier Paolo
PP
Zon
Leonard I
LI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human; C408873:SENP6 protein, human