| First Author | Cui D | Year | 2020 |
| Journal | Cell Death Differ | Volume | 27 |
| Issue | 3 | Pages | 1119-1133 |
| PubMed ID | 31406304 | Mgi Jnum | J:293243 |
| Mgi Id | MGI:6450252 | Doi | 10.1038/s41418-019-0402-x |
| Citation | Cui D, et al. (2020) The cross talk of two family members of beta-TrCP in the regulation of cell autophagy and growth. Cell Death Differ 27(3):1119-1133 |
| abstractText | beta-transducin repeat-containing protein (beta-TrCP), one of the best-characterized substrate recognition components of the SKP1-CUL1-F-box (SCF) E3 ligase, has two distinct paralogs, beta-TrCP1 and beta-TrCP2, expressed in mammals. Through governing the ubiquitination and degradation of numerous key regulators, beta-TrCP1/2 regulates various cellular physiological and pathological processes. However, whether and how these two proteins cross talk and whether they regulate cell autophagy and proliferation in different manners is completely unknown. Herein, we report that beta-TrCP1 and beta-TrCP2 are the physiological substrates of SCF E3 ligase and target each other for degradation that is dependent on their beta-TrCP degron sequences. Furthermore, glucose deprivation activates AMPK kinase to phosphorylate beta-TrCP1 and promotes the subsequent ubiquitination and degradation of beta-TrCP1 by beta-TrCP2, but does not promote beta-TrCP2 degradation by beta-TrCP1. Finally, we found that beta-TrCP2, not beta-TrCP1, preferentially degrades DEPTOR and REDD1, the inhibitors of mTORC1, to activate mTORC1, leading to autophagy inhibition and cell growth. Thus, our study demonstrates that beta-TrCP1 and beta-TrCP2 mutually target each other for degradation and that beta-TrCP2 acts as a dominant paralog in the regulation of cell autophagy and growth, which might be a promising anticancer target. |
