Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival.

Nature | Jan 7, 2010

MCL1 is essential for the survival of stem and progenitor cells of multiple lineages, and is unique among pro-survival BCL2 family members in that it is rapidly turned over through the action of ubiquitin ligases. B- and mantle-cell lymphomas, chronic myeloid leukaemia, and multiple myeloma, however, express abnormally high levels of MCL1, contributing to chemoresistance and disease relapse. The mechanism of MCL1 overexpression in cancer is not well understood. Here we show that the deubiquitinase USP9X stabilizes MCL1 and thereby promotes cell survival. USP9X binds MCL1 and removes the Lys 48-linked polyubiquitin chains that normally mark MCL1 for proteasomal degradation. Increased USP9X expression correlates with increased MCL1 protein in human follicular lymphomas and diffuse large B-cell lymphomas. Moreover, patients with multiple myeloma overexpressing USP9X have a poor prognosis. Knockdown of USP9X increases MCL1 polyubiquitination, which enhances MCL1 turnover and cell killing by the BH3 mimetic ABT-737. These results identify USP9X as a prognostic and therapeutic target, and they show that deubiquitinases may stabilize labile oncoproteins in human malignancies.

Pubmed ID: 20023629 RIS Download

Mesh terms: Animals | Apoptosis | Biphenyl Compounds | Cell Line | Cell Line, Tumor | Cell Survival | DNA Damage | Etoposide | Female | Gene Expression Regulation, Neoplastic | Gene Knockdown Techniques | Half-Life | Humans | Lysine | Mice | Mice, SCID | Myeloid Cell Leukemia Sequence 1 Protein | Neoplasms | Nitrophenols | Phosphorylation | Piperazines | Polyubiquitin | Prognosis | Protein Binding | Protein Stability | Proto-Oncogene Proteins c-bcl-2 | RNA Interference | Sulfonamides | Taxoids | Ubiquitin Thiolesterase | Ubiquitination | Ultraviolet Rays | Xenograft Model Antitumor Assays

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants


Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.