NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets.
Autophagy is an evolutionary conserved cell survival process for degradation of long-lived proteins, damaged organelles and protein aggregates. The mammalian proteins p62 and NBR1 are selectively degraded by autophagy and can act as cargo receptors or adaptors for the autophagic degradation of ubiquitinated substrates. Despite differing in size and primary sequence, both proteins share a similar domain architecture containing an N-terminal PB1 domain, a LIR motif interacting with ATG8 family proteins, and a C-terminal UBA domain interacting with ubiquitin. The LIR motif is essential for their autophagic degradation, indicating that ATG8 family proteins are responsible for the docking of p62 and NBR1 to nucleating autophagosomes. p62 and NBR1 co-operate in the sequestration of misfolded and ubiquitinated proteins in p62 bodies and are both required for their degradation by autophagy. Here we discuss the role of p62 and NBR1 in degradation of ubiquitinated cargoes and the putative role of LIR as a general motif for docking of proteins to ATG8 family proteins.
Lamark
Trond
T
Biochemistry Department, Institute of Medical Biology, University of Tromsø, Tromsø, Norway.
Kirkin
Vladimir
V
Dikic
Ivan
I
Johansen
Terje
T
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D001343:Autophagy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C549756:NBR1 protein, human; D011506:Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin