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The hGID GID4 E3 ubiquitin ligase complex targets ARHGAP11A to regulate cell migration

ABSTRACT: The human GID (hGID) complex is a key E3 ligase regulating multiple cellular processes, including cell cycle progression and metabolic activity. However, the biological functions controlled by hGID remain poorly investigated. Here, we show that the hGID substrate receptor GID4 regulates cell migration and growth. Biochemical and cellular assays combined with proximity-dependent biotinylation (BioID2) uncovered that GID4 targets ARHGAP11A for degradation. Knockdown of GID4 or inhibition of the GID4 substrate binding pocket impairs motility and directed cell movement, whereas abrogation of ARHGAP11A significantly rescues this cell migration defect. GID4 inhibits cell migration by degrading ARHGAP11A thereby preventing its accumulation at the cell periphery where it turns off RhoA activity. Moreover, our BioID2-GID4 screens revealed a variety of substrate profiles beyond Pro/N-degron motifs with functions in microtubule binding, cytoskeletal dynamics and other biological processes. Overall, we identified cellular functions and a wide range of physiological hGID degradation substrates, which paves the way for deciphering molecular pathways regulated by hGID E3 ligase activity through its GID4 substrate receptor.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Hela Cell

DISEASE(S): Cervix Carcinoma

SUBMITTER: Halil Bagci

LAB HEAD: Matthias Peter

PROVIDER: PXD054003 | Pride | 2024-09-24

REPOSITORIES: Pride

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			Action	DRS
	200925_QE1_MP_02_001_fi.mzML	Mzml
	200925_QE1_MP_02_001_fi.raw	Raw
	200925_QE1_MP_02_001_fi_F071598.dat	Other
	200925_QE1_MP_02_003_fi.mzML	Mzml
	200925_QE1_MP_02_003_fi.raw	Raw

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