Selective degradation of p62 by autophagy.
The autophagy-lysosome pathway is a highly conserved bulk degradation system in eukaryotes. During starvation, cytoplasmic constituents are non-selectively degraded by autophagy, and the resulting amino acids are utilized for cell survival. By taking advantage of mouse genetics, many physiological functions of mammalian autophagy have been uncovered. Growing lines of evidences have revealed the essential role of constitutive (or basal) autophagy in cellular homeostasis through its selectivity. p62, one of the selective substrates for autophagy, plays a key role in the formation of cytoplasmic proteinaceous inclusion, a hallmark of conformational diseases such as Alzheimer's disease, Parkinson's disease, and various chronic liver disorders. In this review, we discuss the physiological roles of the selective turnover of p62 by autophagy and their molecular mechanisms.
Ichimura
Yoshinobu
Y
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
Komatsu
Masaaki
M
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000276:immunology*; D002908:Chronic Disease; D006801:Humans; D002479:Inclusion Bodies / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010300:Parkinson Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000071456:Sequestosome-1 Protein
D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein
FEBS Lett. 1993 Oct 25;333(1-2):169-74
8224160
Nat Med. 2007 May;13(5):619-24
17450150
Mol Cell. 2009 Feb 27;33(4):505-16
19250911
J Cell Biol. 2005 May 9;169(3):425-34
15866887
Cell. 2007 Dec 14;131(6):1149-63
18083104
Cancer Cell. 2008 Apr;13(4):343-54
18394557
J Cell Sci. 2008 Aug 15;121(Pt 16):2685-95
18653543
Genes Cells. 2008 Dec;13(12):1211-8
19021777
Cell. 2009 May 15;137(4):721-35
19427028
J Biol Chem. 2008 Aug 15;283(33):22847-57
18524774
Mol Biol Cell. 2008 May;19(5):2092-100
18321988
Am J Hum Genet. 2002 Jun;70(6):1582-8
11992264
Exp Mol Pathol. 2004 Dec;77(3):168-75
15507232
Nature. 2004 Dec 23;432(7020):1032-6
15525940
Science. 2008 Jul 4;321(5885):117-20
18599786
Nat Cell Biol. 2010 Mar;12(3):213-23
20173742
Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-22
9240432
Genes Dev. 2007 Nov 15;21(22):2861-73
18006683
Nat Rev Mol Cell Biol. 2009 Jul;10(7):458-67
19491929
Mol Cell. 2006 Sep 1;23(5):631-40
16949360
Nature. 2006 Jun 15;441(7095):880-4
16625205
J Neurochem. 2004 Oct;91(1):57-68
15379887
Cell. 2007 Jul 13;130(1):165-78
17632063
Cell Metab. 2008 Oct;8(4):325-32
18840363
Nature. 2006 Jun 15;441(7095):885-9
16625204
Cell Death Differ. 2007 May;14(5):887-94
17332773
J Cell Biol. 2008 Dec 1;183(5):795-803
19029340
Nat Cell Biol. 2010 Feb;12(2):119-31
20098416
Brain Res. 2004 Jun 25;1012(1-2):42-51
15158159
J Biol Chem. 2007 Aug 17;282(33):24131-45
17580304
EMBO J. 2009 May 6;28(9):1341-50
19322194
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19500-5
18048346
J Cell Biol. 2005 Nov 21;171(4):603-14
16286508
PLoS Biol. 2010 Jan 26;8(1):e1000298
20126261
EMBO Rep. 2010 Jan;11(1):45-51
20010802
Nature. 2003 Dec 18;426(6968):895-9
14685250
EMBO J. 2000 Nov 1;19(21):5720-8
11060023
Nature. 2008 Jul 10;454(7201):232-5
18454133
Curr Top Microbiol Immunol. 2009;335:1-32
19802558