Table 1.
DYRK2 molecular mechanism and substrates/partners listed along with reported phosphorylation sites, overarching role, and the unanswered questions raised by each study
| Cancer | Molecular partner | Phosphosite | Reported role | Pending question/issue |
|---|---|---|---|---|
| Breast | 26S proteasome/RPT3 (10, 25, 26) | Thr25 | Oncogenic; regulates proteostasis | Data specific for triple-negative breast cancer subtype. |
| HSF1 (11) | Ser320, Ser326 | Data specific for triple-negative breast cancer subtype; possible redundancy with other kinases. | ||
| SNAIL (83) | Ser104 | Tumor suppressor; EMT downregulation | Data heavily reliant on ectopic overexpression; possible redundancies with other kinases | |
| NOTCH1 (31) | Thr2512 | Tumor suppressor; reduces invasion | Redundancies with other kinases; C-Myc pSer62 can be oncogenic; redundancies with other kinases; small sample sizes used for in vivo work. | |
| C-Myc (14) | Ser62 | |||
| C-Jun (14) | Ser243 | Possible redundancies with other DYRK family kinases | ||
| p53 (12, 13) | Ser46 | Tumor suppressor; proapoptotic upon genotoxic stress | Most tumors are p53 mutated/null and mutated p53 becomes oncogenic; DYRK2 mRNA strongly overexpressed in breast cancer overall. | |
| CDK14 (129) | n/a | Tumor suppressor; reduces invasion and proliferation | No specific mechanism reported on how DYRK2 regulates CDK14 transcription. | |
| Lung | SIAH2 (86) | Ser16, Thr26, Ser28, Ser68, Thr119 | Tumor suppressor; modulates hypoxia response pathways | DYRK2 is strongly overexpressed in lung adenocarcinoma; redundancies with other kinases |
| Ovarian | With EDVP/EDD only (89) | n/a | Oncogenic; degrades proapoptotic MOAP1; chemoresistance | Phosphorylated substrate (if any) not established. |
| SNAIL (68) | Ser104 | Tumor-suppressor; EMT downregulation; chemoresistance | Data heavily reliant on ectopic overexpression; possible redundancies with other CMGC kinases; 2 cell lines used only. | |
| Brain | PI3K/AKT/GSK3β (65) | n/a | Tumor-suppressor; EMT downregulation | DYRK2 mRNA is strongly overexpressed in glioma; DYRK inhibitors kill glioma cells. |
| Unknown (unbiased multiomics) (34) | Oncogenic; DYRK2 increased activity and rewired signaling | Multiomics data derived from p53 null murine glioma models; no direct mechanism studied. | ||
| Multiple myeloma | 26S proteasome/RPT3 (25, 26) | Thr25 | Oncogenic; regulates proteostasis | n/a |
| Leukemia | p53/c-myc/KLF4 (72) | n/a | Tumor suppressor; reduces cancer stemness | Data specific for chronic myeloid leukemia subtype. |
| Liver | p53/c-myc (62, 64, 130) | n/a | Tumor suppressor; EMT downregulation; reduces invasion; chemoresistance | p53 and c-Myc have extensive oncogenic mutations reported in liver cancer. |
| LNC-HC/hsa-miR-183-5p (104) | Tumor suppressor; transcriptional upregulation of DYRK2 | Multiple tumor suppressors upregulated including DYRK2; no specific DYRK2 mechanism reported. | ||
| Colorectal | p53 (12) | Ser46 | Tumor suppressor; proapoptotic upon genotoxic stress | Most colorectal tumors are p53 mutated/null, and mutated p53 becomes oncogenic; DYRK inhibitor promotes p53 phosphorylation. |
| DNMT1 (103) | n/a | Tumor suppressor; epigenetic downregulation of DYRK2 | No specific DYRK2 mechanism reported. | |
| miR-622 (63) | Tumor suppressor; EMT downregulation; reduces invasion | |||
| Lymphoma | CDK2/p27Kip1 (73) | n/a | Tumor suppressor; EMT downregulation; chemoresistance | Data specific for non-Hodgkin's lymphoma subtype. |
CMGC, Cyclin-dependent kinases, Mitogen-activated protein kinases, Glycogen synthase kinases, and CDC-like kinases; DYRK, Dual-specificity tYrosine phosphorylation–Regulated Kinase; EMT, epithelial–mesenchymal transition; HSF1, heat-shock factor 1; MOAP, modulator of apoptosis protein 1; NOTCH1, neurogenic locus notch homolog protein 1; n/a, not directly reported.
Also, refer Figure 3.