High impact information on UBR1

• RAD6 interacts physically with the UBR1 gene product in carrying out the multiubiquitination of amino-end rule proteolytic substrates [1].
• We previously showed that UBR1 and UFD4, two E3 ligases of the yeast Saccharomyces cerevisiae, interact with specific proteasomal subunits [2].
• These results defined the topography of the Ubc2p-Ubr1p interaction and revealed the essential function of the RING-H2 finger, a domain that is present in many otherwise dissimilar E3 proteins of the ubiquitin system [3].
• The Ubr1p-Cup9p-Ptr2p circuit is the first example of a physiological process controlled by the N-end rule pathway [4].
• In contrast to engineered N-end rule substrates, which are recognized by Ubr1p through their destabilizing N-terminal residues, Cup9p is targeted by Ubr1p through an internal degradation signal [4].

Biological context of UBR1

• TYS1 was reported previously to lie on chromosome XV based on sequence overlap with the adjacent UBR1 gene [5].
• We demonstrated, through in vivo and in vitro assays, that Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase, which was originally identified as a sequence homolog of Ubr1, the E3 component of the N-end rule pathway [6].

Anatomical context of UBR1

• The decreased mass of UBR1(-/-) mice stemmed at least in part from smaller amounts of the skeletal muscle and adipose tissues [7].
• By contrast, and despite the absence of the UBR1 protein, UBR1(-/-) fibroblasts contained the N-end rule pathway [7].

Associations of UBR1 with chemical compounds

• This defect in histidine uptake, exhibited by the sln2 mutant in the absence but not in the presence of Ubr1p, was traced to the gene HIP1, which encodes the histidine transporter [8].

Physical interactions of UBR1

• A ptr1-1 rae1-167 double mutant showed a synthetic effect on a growth defect, indicating that Ptr1p functionally interacts with an essential mRNA export factor Rae1p [9].

Other interactions of UBR1

• Previous work demonstrated that dipeptides with destabilizing N-terminal residues allosterically activate UBR1, leading to accelerated in vivo degradation of CUP9 and the induction of PTR2 expression [10].
• Previous studies have indicated the involvement of N-terminal and C-terminal regions of Rad6 in interactions with Ubr1 [11].
• Yet another property of the sln2 mutant was its inviability at 37 degrees C, which could not be rescued by either UBR1 or HIS3 [8].
• Our findings show that peptide transport and the ubiquitin pathway--two dynamic phenomena universal to eukaryotic cells--share a common component, namely UBR1/PTR1 [12].
• The PTR system consists of three genes, PTR1, PTR2 and PTR3 [13].
• A third substrate-binding site of UBR1 targets an internal degron of CUP9, a transcriptional repressor of peptide import [14].

References