NFE2L1 is an endoplasmic reticulum membrane sensor which, in response to various stresses, it is released from the ER membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1 []. In conditions of excess cholesterol, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, this allows the expression of genes promoting cholesterol removal []. In response to oxidative stress, Nrf1 up-regulates expression of antioxidant genes by binding to the antioxidant response elements (AREs) present in the promoter of these genes []. In humans Nrf1 exists in two forms, p120 and p110. p120 is embedded in the ER membrane, while p110 is soluble and can enter the nucleus [, ].
Reticulophagy regulator 3 (RETREG3), also known as FAM134C, mediates NRF1-enhanced neurite outgrowth. NRF1 (nuclear respiratory factor-1) is a major transcription factor that can positively regulate FAM134C []. Members of the FAM134 protein family, including FAM134C, are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy [].
This domain is found in plants and higher eukaryotes, and is the N-terminal region of micro-spherule proteins which repress the transactivation activities of Nrf1 (p45 nuclear factor-erythroid 2 (p45 NF-E2)-related factor 1) []. In conjunction with DIPA the full-length protein acts as a transcription repressor []. The exact function of this domain is not known.
This entry include reticulophagy receptor 1 and reticulophagy receptor 3.Reticulophagy receptor 1, previously known as FAM134B, is essential for endoplasmic reticulum (ER) homeostasis. It is a ER resident receptor that binds to autophagy modifiers LC3 and GABARAP, and facilitates ER degradation by autophagy. It may promote membrane remodelling and ER scission via the membrane-bending capacity of its reticulon domain, whereas its LIR motif may be necessary to target the ER fragments to autophagosomes for lysosomal degradation [].Reticulophagy regulator 3 (RETREG3), also known as FAM134C, mediates NRF1-enhanced neurite outgrowth. NRF1 (nuclear respiratory factor-1) is a major transcription factor that can positively regulate FAM134C []. Members of the FAM134 protein family, including FAM134C, are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy [].
