SUMO-1 conjugation in normal and stress conditions in vivo

................................................................................................................. 5 YHTEENVETO ............................................................................................................. 7 ORIGINAL PUBLICATIONS ...................................................................................... 9 ABBREVIATIONS ..................................................................................................... 10 INTRODUCTION ....................................................................................................... 12 REVIEW OF THE LITERATURE ............................................................................. 13 1. Nuclear receptors as regulators of transcription .................................................. 13 1.1 Transcription factors and their coregulators .................................................. 13 1.2 The nuclear receptor superfamily .................................................................. 15 1.3 Transcriptional activation and repression by NRs ......................................... 17 1.4 PPARs ............................................................................................................ 20 1.5 LXR ............................................................................................................... 21 1.6 LRH-1 ............................................................................................................ 22 2. SUMOylation pathway ........................................................................................ 23 2.1 Sumo1-4 ......................................................................................................... 23 2.2 E3 enzymes .................................................................................................... 25 2.3 SENPs ............................................................................................................ 27 2.4 Consensus motifs for SUMO conjugation and recognition ........................... 27 2.5 Crosstalk with other modifications ................................................................ 28 3. Functions of SUMOylation ................................................................................. 30 3.1 Regulation of transcription ............................................................................ 31 3.2 Regulation of inflammation ........................................................................... 35 3.3 Stress and SUMO .......................................................................................... 36 3.4 SUMO and chromosomal stability ................................................................ 37 3.5 SUMO and human diseases ........................................................................... 39 4. Adipose tissue ...................................................................................................... 40 4.1 White adipose tissue ...................................................................................... 41 4.2 Brown adipose tissue ..................................................................................... 42 4.3 Obesity ........................................................................................................... 43 5. Testis .................................................................................................................... 44 5.1 Development .................................................................................................. 45 5.2 Spermatogenesis ............................................................................................ 46 AIMS OF THE STUDY .............................................................................................. 49 MATERIALS AND METHODS ................................................................................ 50 RESULTS AND DISCUSSION .................................................................................. 58