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TBC1D22B Regulates ER-to-Golgi Trafficking via RAB1B Inactivation and Promotes Oncogenic Programs in Breast Cancer

ABSTRACT: The anterograde secretory pathway shapes the extracellular environment and the ability of cells to communicate, through the release of cytokines, growth factors, enzymes and extracellular matrix components, and through the regulation of the composition of the plasma membrane (PM). The underlying molecular machinery operates in a concerted and highly regulated manner and is frequently altered in cancer. The Golgi RabGAP protein TBC1D22B is overexpressed in breast cancer and predicts prognosis. Herein, deconvolution of the proximity-labeling and physical interactomes of TBC1D22B, reveals its role in the regulation of anterograde trafficking with liaisons with networks of proteins involved in cell adhesion, and in carbohydrate and lipid metabolism. The function of TBC1D22B in the anterograde pathway was formally demonstrated using the Retention Using Selective Hooks system which synchronizes transport of cargoes from the ER to the Golgi and the PM. TBC1D22B inhibits ER to Golgi transport in a GAP-dependent manner. RAB1B, a key RAB in the early secretory pathway, was found to be a substrate of the TBC1D22B GAP activity, and its silencing phenocopied TBC1D22B overexpression. Thus, TBC1D22B regulates ER to Golgi trafficking through its ability to work as a GAP for RAB1B.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: alessandro cuomo

LAB HEAD: Letizia Lanzetti

PROVIDER: PXD060457 | Pride | 2025-08-21

REPOSITORIES: Pride

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	HF211018_PPDF_TBC1D722B_EV_01.raw	Raw
	HF211018_PPDF_TBC1D722B_EV_02.raw	Raw
	HF211018_PPDF_TBC1D722B_EV_03.raw	Raw
	HF211018_PPDF_TBC1D722B_EV_04.raw	Raw
	HF211018_PPDF_TBC1D722B_EV_H2O2_01.raw	Raw

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