Functional analysis of the sumoylation pathway in Saccharomyces cerevisae
Final Report Abstract
Post-translational modifications provide a rapid and efficient means by which properties of proteins can be modulated in response to the cellular state or its environment. The modifiers include small organic/inorganic molecules: acetyl, phosphate etc. and entire proteins: ubiquitin and ubiquitin-like proteins (Ubi). The reversible and covalent attachment to large number of proteins involved in diverse cellular processes makes SUMO (small ubiquitin related modifier) the most intriguing Ubi. Our proteomic approach revealed that the majority of the proteins modified by SUMO are nuclear and part of large dynamic macromolecular complexes involved in DNA replication and repair, chromatin remodeling, transcription, mRNP (mRNA ribonucleoprotein complexes) formation, ribosome biogenesis etc. In this proposal we have shown that all three-transcription machiienries are subject to SUMO modification. Additionally, we have shown that a functional SUMO pathway is required for proper ribosome biogensis and their nuclear export. Moreover, we found that the SUMO conjugation machinery pathway is functionally linked to early nucleolar ribosome biogenesis whereas the desumolyation machinery localized at the nuclear pore complex is functionally linked to factors required for their nuclear export. Consistent with these observations, we have shown that several nucleolar factors that are involved in early biogenesis of ribosomal subunits are subject to SUMO modification. Thus our findings underscore the requirement of the SUMO pathway in assembly/disassembly of important large macromolecular complexes involved in diverse nuclear pathways and represent an important step towards understanding the essential pathways regulated by SUMO modification.
Publications
- A proteome-wide approach identifies sumoylated substrate proteins in yeast. J Biol Chem. 2004 Oct 1;279(40):41346-51
Panse VG, Hardeland U, Werner T, Kuster B, Hurt E
- Coordinated nuclear import of RNA polymerase III subunits. Traffic. 2006 Apr;7(4):465-73
Hardeland U, Hurt E
- Formation and nuclear export of preribosomes are functionally linked to the small-ubiquitin-related modifier pathway. Traffic. 2006 Oct;7(10):1311-21
Panse VG, Kressler D, Pauli A, Petfalski E, Gnädig M, Tollervey D, Hurt E
- Adjunct duties for karyopherins: regulating septin sumoylation. Dev Cell. 2007 May;12(5):669-70
Panse VG, Hurt E
