Table 1 Posttranslational modification of ferroptosis by ubiquitination in cancer
Cancer | Modification | Targets | E3s | DUBs | Biological functions | Ref |
|---|---|---|---|---|---|---|
HCC | Ubiquitination | SLC7A11 | - | - | SOCS2-enhanced ubiquitination of SLC7A11 promotes ferroptosis and radiosensitization in HCC. | |
HCC | Ubiquitination | SLC7A11 | RNF182 | - | p53-induced increase of PCDHB14 downregulates the expression of SLC7A11 thereby promoting ferroptosis and is a novel tumor suppressor in HCC. PCDHB14 promoting E3 ubiquitin ligase RNF182-mediated ubiquitination of p65 to block p65 binding to the promoter of SLC7A11. | |
HCC | Ubiquitination | EGFR/Nrf2 | - | QSOX1 promotes sorafenib-induced ferroptosis in HCC by driving ubiquitination-mediated degradation of EGFR, leading to suppression of Nrf2 activation. | ||
HCC | Ubiquitination | TfRC | βTrCP | - | TRIB2 inhibit ferroptosis via βTrCP-mediated TfRC ubiquitiantion in liver cancer cells | |
HCC | Ubiquitination | FSP1 | TRIM69 | HDLBP-stabilized lncFAL inhibits ferroptosis vulnerability by diminishing Trim69-dependent FSP1 degradation in HCC. | ||
GC | Ubiquitination | Nrf2 | TRPM2 | - | Silencing TRPM2 enhanced ferroptosis in gastric cancer cells through destabilizing HIF-1α and Nrf2 proteins. | |
GC | Ubiquitination | VDAC3 | FBXW7 | - | LncRNA BDNF-AS inhibit ferroptosis through recruiting WDR5 to transcriptionly upregulate FBXW7, thereby mediating ubiquitiantion-dependent degradation of VDAC3 and promoted the progression of GC. | |
GC | Ubiquitination | GPX4 | OTUB1 | - | CST1 promotes gastric cancer metastasis by inhibits ferroptosis through inhibiting OTUB1-mediated GPX4 ubiquitination and degradation. | |
GC | Ubiquitination | ALOX15 | - | USP7 | Cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and ferroptosis in cancer cells, and ultimately result in decreased chemosensitivity. | |
CRC | Ubiquitination | Nrf2 | - | - | LINC00239 inhibits ferroptosis in CRC by binding to Keap1 to stabilize Nrf2. | |
CRC | Ubiquitination | P53/GPX4 | MDM2 | USP11 | RRM1 deficiency impairs the stability of p53 and sensitizes different types of cancer cells to ferroptosis by reducing GPX4 expression. Knockdown of RRM1 stimulates the binding of the MDM2 and p53 while inhibiting the binding of USP11 to p53, thereby increasing the ubiquitination of p53. The instability of p53 results in lower expression of p21, which causes ferroptosis and a decrease in cell survival time by inhibiting GPX4. | |
CCA | Ubiquitination | GPX4 | - | - | FBXO31 as a tumor suppressor sensitizes CSC-like cells to CDDP by promoting ferroptosis and facilitating the proteasomal degradation of GPX4. functions as a tumor. | |
CCA | Ubiquitination | p53/SLC7A11/GPX4 | - | - | SHARPIN promotes cell proliferation through inhibiting ferroptosis via promoting the ubiquitination and degradation of p53, and upregulating SLC7A11/GPX4. | |
NSCLC | Ubiquitination | SLC7A11 | - | USP7 | Erastin induce ferroptosis through decreasing the levels of H2Bub1 that epigenetically activates the expression of SLC7A11. p53 negatively regulates H2Bub1 levels by promoting the nuclear translocation of the deubiquitinase USP7. p53 decreases H2Bub1 occupancy on the SLC7A11 gene regulatory region and represses the expression of SLC7A11 during erastin treatment. | |
NSCLC | Ubiquitination | SLC1A5 | TRIM6 | - | TRIM6 directly interacted with SLC1A5 to promote its ubiquitination and degradation, thereby inhibiting glutamine import, glutaminolysis, lipid peroxidation, and ferroptosis. | |
NSCLC | Ubiquitination | FPN | - | USP35 | USP35 directly interacted with ferroportin (FPN) and functioned as a deubiquitinase to maintain its protein stability. USP35 knockdown sensitized lung cancer cells to cisplatin and paclitaxel chemotherapy. | |
NSCLC | Ubiquitination | Nrf2 | - | USP11 | Elevated USP11 promote NSCLC cancer cell proliferation through inhibiting ferroptosis via deubiquitinates and stabilizes Nrf2. | |
GBM | Ubiquitination | NCOA4 | TRIM7 | - | Elevated expression of TRIM7 in human glioblastoma. Silenced TRIM7 suppressed growth through inducing ferroptosis, while TRIM7overexpression inhibited ferroptosis. TRIM7 directly bound to and ubiquitinated nuclear receptor coactivator 4 (NCOA4), thereby reducing NCOA4-mediated ferritinophagy and ferroptosis of human glioblastoma cells. Moreover, we found that TRIM7 deletion sensitized human glioblastoma cells to temozolomide therapy. | |
GBM | Ubiquitination | p53/SLC7A11 | - | - | RND1 induce ferroptosis through interacting and de-ubiquitinating p53, thereby inhibiting SLC7A11 in GBM. | |
GBM | Ubiquitination | PRRX2/GCH1 | - | - | Downregulated circLRFN5 promote malignancy through inhibiting ferroptosis in GBM. CircLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway, thereby transcriptionally upregulating GCH1 expression in GSCs, which is a ferroptosis suppressor | |
ccRCC | Ubiquitination | SLC7A11 | BAP1 | - | BAP1 decreases H2Aub occupancy on the SLC7A11 promoter and represses SLC7A11 expression in a deubiquitinating-dependent manner, and that BAP1 inhibits cystine uptake by repressing SLC7A11 expression, leading to elevated lipid peroxidation and ferroptosis. | |
ccRCC | Ubiquitination | SLC7A11 | BAP1/PRC1 | BAP1 promotes erastin-induced ferroptosis through repressing SLC7A11 expression. BAP1 decreases whereas PRC1 (a major H2Aub ubiquitin ligase) increases H2Aub binding on the SLC7A11 promoter, both BAP1 and PRC1 represses SLC7A11 expression. | ||
OC | Ubiquitination | HMOX1 | TRC8 | - | MTHFR inhibits TRC8-mediated HMOX1 ubiquitination thereby blocking ferroptosis and promote the tumor cells growth. | |
OC | Ubiquitination | SLC7A11 | HRD1 | - | HRD1 functions as a tumor suppressor by facilitating ubiquitination-dependent SLC7A11 degradation in ovarian cancer. | |
BC | Ubiquitination | CD71 | NEDD4L | - | Estrogen receptor 1 (ESR1) promote cancer through inhibiting ferroptosis in breast cancer cells via the NEDD4L-mediated ubiquitination and degradation of CD71. | |
Bladder Cancer | Ubiquitination | SLC7A11 | - | - | PHGDH interact with PCBP2 to inhibit its ubiquitination degradation, upregulates SLC7A11 and thereby inhibits ferroptosis and promotes malignant progression. | |
ALL | Ubiquitination | Nrf2 | - | - | PAQR3 inhibits proliferation and aggravates ferroptosis in acute lymphoblastic leukemia through increasing Nrf2 degradation. | |
ALL | Ubiquitination | VDAC3 | FBXW7 | - | Autophagy activation sensitized ALL cells to erastin-induced ferroptosis through inhibiting FBXW7-mediated ubiquitiantion-dependant degradation of VDAC3. | |
Melanoma | Ubiquitination | VDAC2/3 | Nedd4 | - | Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma. | |
Fibrosarcoma | Ubiquitination | Nrf2 | - | - | CISD2 knockdown promoted the degradation of autophagy adaptor p62 and resulted in an increased Keap1-mediated Nrf2 ubiquitination and subsequent degradation. |
