UBQLN Family Members Regulate MYC in Lung Adenocarcinoma Cells.

The ubiquilin family (UBQLN) of proteins consists of five closely related members (UBQLN1, UBQLN2, UBQLN3, UBQLN4, and UBQLNL) that have a high degree of similarity at the level of both amino acid and domain structure. The role of UBQLN1 and UBQLN2 in regulating processes involved in cancer progression and tumorigenesis is still not completely understood. MYC is an oncogene and is well known to play important roles in cancer progression and metastasis. Herein, we show that the loss of UBQLN1 and UBQLN2 causes increased cell viability, cell proliferation, cell migration, clonogenic potential, and cell cycle progression, which is associated with increased MYC expression. UBQLN1 and UBQLN2 interact with phosphorylated MYC and facilitate its degradation. The overexpression of UBQLN1 reverses the increased expression of MYC following the loss of UBQLN2. Further, we present evidence that decreasing MYC levels back to baseline can reverse phenotypes driven by the loss of UBQLN1 or UBQLN2. Finally, we show that loss of UBQLN1 drives tumorigenesis and lung metastasis in mice which are associated with an increase in the expression of MYC, proteins involved in cell cycle progression, and EMT. Taken together, our results suggest for the first time a novel role of UBQLN1 and UBQLN2 in regulating MYC in lung adenocarcinoma cells.

Citation

Parag P Shah, Levi J Beverly. UBQLN Family Members Regulate MYC in Lung Adenocarcinoma Cells. Cancers. 2023 Jun 28;15(13)

PMID: 37444499

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