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. Author manuscript; available in PMC: 2012 Jul 1.
Published in final edited form as: Cancer Prev Res (Phila). 2011 Jul;4(7):973–983. doi: 10.1158/1940-6207.CAPR-10-0387

Figure 2. Role of autophagic regulation of p62 in cell signaling.

Figure 2

Stress upregulates autophagy and also induces the accumulation of the autophagic cargo receptor protein p62. Autophagy regulates p62 turnover and its protein levels in cells (denoted by an asterisk). Domains of p62 are depicted diagrammatically. PB1: Phox and Bem1p-1 oligomerization domain. ZZ: zinc finger. TBS: TRAF6-binding sequence. LIR: LC3-interacting region. KIR: Keap1-interacting region. UBA: ubiquitin-associated domain. Numbers represent the corresponding amino acid positions in mouse p62. NLS: nuclear localization signal. NES: nuclear export signal (40, 43, 76). Brown arrows indicate p62-protein interactions. The dash indicates a putative interaction between p62 and ERK (77). Accumulation of p62 activates Nrf2, while p62 itself is a transcriptional target of Nrf2, creating a positive feedback loop (45). Green or red depicts signals occurring when p62 loses or gains function, respectively. The dashed green line shows a putative role of obesity in tumorigenesis (see Fig. 3). The dashed red line shows a putative consequence of hyperactive Nrf2.