Regulation of the anaphase promoting complex/cyclosome by the degradation of its unassembled catalytic subunit, Apc11

Abstract

One of the challenges encountered by the protein quality control machinery is the need to ensure that members of multiprotein complexes are available in the correct proportions. In this study, we demonstrate that the ubiquitin proteasome system (UPS) mediates the degradation of Apc11, the catalytic core subunit of the anaphase promoting complex/cyclosome (APC/C). In vitro studies have shown that Apc11, together with its E2 enzyme, is sufficient to ubiquitinate substrates independently of the APC/C. Here, we establish that this can occur in living yeast cells. We show that the tight controls regulating the function of the fully assembled APC/C can be circumvented when its substrates are ubiquitinated by the excess levels of Apc11 independently of the assembled complex. We thus suggest that the UPS‐mediated degradation of Apc11 is an overlooked mechanism ensuring that proper function of the APC/C is limited to suitably delimited holoenzymes and that an imbalance in protein expression may result in detrimental gain‐of‐function activity, rather than merely the disruption of protein complex stoichiometry.—Volpe, M., Levinton, N., Rosenstein, N., Prag, G., Ben‐Aroya, S. Regulation of the anaphase promoting complex/cyclosome by the degradation of its unassembled catalytic subunit, Apc11. FASEB J. 33, 9752–9761 (2019). http://www.fasebj.org

Plant E3 Ligases and Their Role in Abiotic Stress Response

“…This class of E3 ligases is known for DNA damage and abiotic stress responses, as well as photomorphogenesis [ 47 , 48 , 49 ]. Finally, the Anaphase Promoting Complex/Cyclosome (APC/C) is required for sister chromatid separation in anaphase, and DNA replication processes in S-phase, but it also has been brought into context with auxin signaling [ 50 , 51 ].…”

The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer

“…Previous studies have established that ANAPC11 is the catalytic core subunit of APC/C and functions as an E3 ubiquitin ligase [ 39 ]. We investigated whether ANAPC11 regulates UBC cell growth and metastasis through the ubiquitin‒proteasome system (UPS).…”

RPS12 and UBC4 Are Related to Senescence Signal Production in the Ribosomal RNA Gene Cluster

“…Ubiquitination is well known as a marker for degradation of the modified protein by the proteasome, but it also functions in various cellular processes such as signals for cell cycle control, protein trafficking, and epigenetic regulation ( 47 , 48 ). UBC4 has a paralogue, UBC5 , and is involved in the regulation of the cell cycle via APC, that can target Fob1, and helps to control other processes through interaction with a variety of E3 ligases ( 22 , 33 , 34 ).…”

“…The UBC4 gene-product acts as the E2 enzyme for the anaphase promoting complex APC, which is an E3-ligase, and participates in the self-regulation of its catalytic core, subunit Apc11 ( 33 ). The APC complex controls the passage through M and G1 during the cell cycle by ubiquitin dependent targeting of proteins, one of which is Fob1: A subunit of the APC complex, Apc5, is able to physically interact with Fob1 ( 22 ).…”

“…Ubc4 is a ubiquitin-conjugating enzyme (E2), related to protein degradation (reviewed in Ref. 32 ) and, together with its paralog Ubc5, implied in the control of various processes through interaction with various E3 ligases such as APC ( 22 , 33 ) and Tom1, which controls the levels of unincorporated ribosomal proteins ( 34 ). Cells that do not produce Ubc4 have a longer chronological life span, another aspect of yeast aging (for replicative life span and chronological life span, see Ref.…”