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Table 1 Regulators of Keap1-Nrf2 pathway and their biological effects in pancreatic cancer

From: Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review

Regulators Keap1/Nrf2 Biological consequences Refs
Cullin3 Keap1 Forms the Keap1-Cul3-RBX1 E3 ligase complex and induces Nrf2 polyubiquitination and proteasomal degradation [36]
UHRF1 Keap1 Down-regulates Keap1 expression by enhancing KEAP1 promoter methylation [39]
MBD1 Keap1 Down-regulates Keap1 expression by enhancing KEAP1 promoter methylation [40]
p62 Keap1 Directly binds to Keap1, competitively inhibits the binding of Nrf2 to Keap1, and protects Nrf2 from protein degradation [30]
aPKCι Keap1 Directly binds to Keap1, competitively inhibits the binding of Nrf2 to Keap1, and protects Nrf2 from protein degradation [41]
PALB2 Keap1 Directly binds to Keap1, competitively inhibits the binding of Nrf2 to Keap1, and protects Nrf2 from protein degradation [42]
KRAL Keap1 Directly interacts with miR-141 and increases the expression of Keap1 [43]
β-TrCP Nrf2 Directly binds to Nrf2 and promotes its ubiquitination and proteasomal degradation [23]
HRD1 Nrf2 Directly interacts with Nrf2 and promotes its ubiquitination and proteasomal degradation [38]
GSK-3β Nrf2 Phosphorylates Nrf2 at Ser342 and Ser347 in Neh6 domain [23]
ALDOA Nrf2 Increases the expression of Nrf2 [44]
Kras/ERKaxis Nrf2 Increases the expression of Nrf2 [45,46,47]
GRP78/UPR Nrf2 Increases the activity of Nrf2 [48]
STAT3 Nrf2 Increases the expression of Nrf2 [14]
APE1/Ref-1 Nrf2 Directly interacts with Nrf2 and inhibits its activity [49]
dCK Nrf2 Negatively regulates the NRF2 transcriptional activity [50]
NRAL Nrf2 Directly binds to miR-340-5p, inhibits miR-340-5p-mediated repressing activity of the Nrf2–3’UTR, and increases Nrf2 expression [51]