The size of the proteasomal substrate determines whether its degradation will be mediated by mono- or polyubiquitylation.
A polyubiquitin chain anchored to the substrate has been the hallmark of proteasomal recognition. However, the degradation signal appears to be more complex and to contain also a substrate's unstructured region. Recent reports have shown that the proteasome can degrade also monoubiquitylated proteins, which adds an additional layer of complexity to the signal. Here, we demonstrate that the size of the substrate is an important determinant in its extent of ubiquitylation: a single ubiquitin moiety fused to a tail of up to ∼150 residues derived from either short artificial repeats or from naturally occurring proteins, is sufficient to target them for proteasomal degradation. Importantly, chemically synthesized adducts, where ubiquitin is attached to the substrate via a naturally occurring isopeptide bond, display similar characteristics. Taken together, these findings suggest that the ubiquitin proteasomal signal is adaptive, and is not always made of a long polyubiquitin chain.
Cancer and Vascular Biology Research Center, Technion-Israel Institute of Technology, Haifa, Israel.
Nitzan
N
Shabek
Yifat
Y
Herman-Bachinsky
Samuel
S
Buchsbaum
Oded
O
Lewinson
Mahmood
M
Haj-Yahya
Mirva
M
Hejjaoui
Hilal A
HA
Lashuel
Thomas
T
Sommer
Ashraf
A
Brik
Aaron
A
Ciechanover
D000595:Amino Acid Sequence; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
D010455:Peptides; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D025821:Polyubiquitin; D049452:Green Fluorescent Proteins; D046988:Proteasome Endopeptidase Complex