C 1: Mul­tiple me­cha­nisms control­ling the SUMO mo­di­fied state of pro­teins

Prof. Dr. Jürgen Doh­men

Ins­ti­tut für Ge­ne­tik, Uni­ver­sität zu Köln
email: j.​dohmen@​uni-koeln.​de
phone: +49-(0)221 470 4862
web­site

Run­ning time: 2003 – 2011

Abs­tract

Post­trans­la­tio­nal pro­tein mo­di­fi­ca­tion with SUMO is an im­por­tant re­gu­la­tory me­cha­nism im­pli­ca­ted in many cel­lu­lar pro­cesses. We iden­ti­fied two yeast SUMO bin­ding pro­teins that me­diate the pro­teo­ly­tic down­re­gu­la­tion of su­moy­la­ted pro­teins. Poly-su­moy­la­tion and ubi­qui­tin-de­pendent de­gra­da­tion ap­pear to be al­ter­na­tive me­cha­nisms to in­ac­ti­vate su­moy­la­ted pro­teins. In­hi­bi­tion of both me­cha­nisms leads to se­vere phe­no­ty­pic de­fects. Pro­teo­ly­tic control of SUMO conju­gates is conser­ved from yeast to hu­mans. We will ana­lyse the me­cha­nis­tic de­tails and func­tions of ubi­qui­tin-me­dia­ted pro­teo­ly­sis of SUMO sub­strates.

(A final re­port will fol­low.)

Pu­bli­ca­tions re­sul­ting from the pro­ject:

Schnell­hardt, M., Uzu­nova, K., Bade, V.N., Krause, A., Weis­shaar, S.R. Praefcke, G.J.,K., and Doh­men, R.J. (2012). Ana­ly­sis of cel­lu­lar SUMO and SUMO-ubi­qui­tin hy­brid conju­gates. Me­thods in Mo­le­cu­lar Bio­logy 832, 82-91. (re­view)

Praefcke, G.J,K, Hof­mann, K., and Doh­men, R.J. (2012). SUMO playing tag with ubi­qui­tin. Trends in Bio­che­mi­cal Sciences 37, 23-11. (re­view)

Hermkes, R., Fu, Y.F., Nürren­berg, K., Bud­hi­raja, R., Schmel­zer, E., El­rouby, N., Doh­men, R.J., Bach­mair, A., and Cou­pland, G. (2011). Dis­tinct roles for Ara­bi­dop­sis SUMO pro­tease ESD4 and its clo­sest ho­mo­log ELS1. Planta 233, 63-73.

Mi­teva, M., Keu­se­kot­ten, K., Hof­mann, K., Praefcke, G.J.K., and Doh­men, R.J. (2010). Su­moy­la­tion as a si­gnal for po­ly­ubi­qui­ty­la­tion and pro­tea­so­mal de­gra­da­tion. In: Conju­ga­tion and de­con-ju­ga­tion of ubi­qui­tin fa­mily mo­di­fiers, edi­ted by Mar­cus Groet­trup. Landes Bios­cience and Sprin­ger Science+Bu­si­ness Media. pp 195-214.

Weis­shaar, S.R., Keu­se­kot­ten, K., Krause, A., Horst, C., Sprin­ger, H.M., Göttsche, K., Doh­men, R.J., and Praefcke, G.J.K. (2008). Ar­se­nic trioxide sti­mu­lates SUMO-2/3 mo­di­fi­ca­tion lea­ding to RNF4-de­pendent pro­teo­ly­tic tar­ge­ting of PML. FEBS Lett. 582, 3174-3178.

Uzu­nova, K., Göttsche, K., Mi­teva, M., Weis­shaar, S.R., Gla­ne­mann, C., Schnell­hardt, M., Nies­sen, M., Scheel, H., Hoff­mann, K., John­son, E.S., Praefcke, G.J.K. and Doh­men, R.J. (2007). Ubi­qui­tin-de­pendent Pro­teo­ly­tic control of SUMO conju­gates. J. Biol. Chem. 282, 34167-34175.