Dimerization of ubiquilin is dependent upon the central region of the protein: evidence that the monomer, but not the dimer, is involved in binding presenilins.
Ubiquilin proteins have been shown to interact with a wide variety of other cellular proteins, often regulating the stability and degradation of the interacting protein. Ubiquilin contains a UBL (ubiquitin-like) domain at the N-terminus and a UBA (ubiquitin-associated) domain at the C-terminus, separated by a central region containing Sti1-like repeats. Little is known about regulation of the interaction of ubiquilin with other proteins. In the present study, we show that ubiquilin is capable of forming dimers, and that dimerization requires the central region of ubiquilin, but not its UBL or the UBA domains. Furthermore, we provide evidence suggesting that monomeric ubiquilin is likely to be the active form that is involved in binding presenilin proteins. Our results provide new insight into the regulatory mechanism underlying the interaction of ubiquilin with presenilins.
Ford
Diana L
DL
Medical Biotechnology Center, Institute for Neurodegenerative Diseases, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA.
Monteiro
Mervyn J
MJ
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D053764:Presenilin-1; D053766:Presenilin-2; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014452:Ubiquitins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D011993:Recombinant Fusion Proteins; C107792:UBQLN1 protein, human; C405662:UBQLN2 protein, human; D014452:Ubiquitins; D009955:Ornithine Decarboxylase