Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.

Leukemia
A Lopez-GironaRajesh Chopra

Abstract

Thalidomide and the immunomodulatory drug, lenalidomide, are therapeutically active in hematological malignancies. The ubiquitously expressed E3 ligase protein cereblon (CRBN) has been identified as the primary teratogenic target of thalidomide. Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN-DNA damage binding protein-1 (DDB1) complexes. CRBN mediated antiproliferative activities of lenalidomide and pomalidomide in myeloma cells, as well as lenalidomide- and pomalidomide-induced cytokine production in T cells. Lenalidomide and pomalidomide inhibited autoubiquitination of CRBN in HEK293T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplified pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for lenalidomide resistance in H929 myeloma cell lines was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and lenalidomide, CRBN protein was undetectable. O...Continue Reading

References

Jun 1, 1983·Teratology·M Parkhie, M Webb
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·R J D'AmatoJ Folkman
Jan 15, 2002·Journal of Biomolecular Screening·M W PantolianoF R Salemme
Mar 1, 1965·Toxicology and Applied Pharmacology·I D FRATTAK MAIORANA
Apr 2, 2004·Nature Reviews. Cancer·J Blake BartlettAngus G Dalgleish
Mar 24, 2007·Molecular Biology Reports·Wang XinWu Qihan
Jan 27, 2009·FEBS Letters·Bettina Hohberger, Ralf Enz
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Martha Q LacyS Vincent Rajkumar
Feb 6, 2010·Journal of Neurogenetics·Joseph J HigginsAnjali M Rajadhyaksha
Mar 13, 2010·Science·Takumi ItoHiroshi Handa
Aug 7, 2010·Current Opinion in Oncology·Shirong LiSuzanne Lentzsch
Aug 10, 2010·Core Evidence·Paul RichardsonKenneth Anderson
Jan 15, 2011·Biochimica Et Biophysica Acta·Kwang Min LeeChul-Seung Park
Jan 19, 2011·Neuroscience Research·Miho AizawaHiroyuki Nawa
Feb 11, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Annunziata De LuisiAngelo Vacca
Mar 19, 2011·Expert Opinion on Investigational Drugs·Stephen Schey, Karthik Ramasamy
Mar 26, 2011·Annals of the New York Academy of Sciences·Jerome B ZeldisGeorge Muller

❮ Previous
Next ❯

Citations

Jul 5, 2013·Cancer Immunology, Immunotherapy : CII·Wai Man LiuAngus George Dalgleish
Dec 4, 2012·Cancer Chemotherapy and Pharmacology·Matthew HoffmannGondi Kumar
Jun 9, 2012·The Lancet Oncology·Stephen M Ansell
Sep 10, 2013·Blood Cancer Journal·A A Chanan-KhanM Q Lacy
Jul 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Chris MahonyNeil Vargesson
Jan 8, 2013·Japanese Journal of Clinical Oncology·Kenshi Suzuki
Jan 3, 2014·The Journal of Clinical Investigation·Nathaniel M Weathington, Rama K Mallampalli
Aug 28, 2013·Seminars in Cancer Biology·Patricia Amé-Thomas, Karin Tarte
Jul 11, 2013·Future Oncology·Peter A Forsberg, Tomer M Mark
Jan 1, 2014·Acta Biochimica Et Biophysica Sinica·Xiubao ChangA Keith Stewart
Aug 12, 2014·Nature Structural & Molecular Biology·Philip P ChamberlainBrian E Cathers
Jul 19, 2014·Nature Reviews. Drug Discovery·John G MoffatDavid Bailey
Jul 22, 2014·Nature·Eric S FischerNicolas H Thomä
Apr 11, 2015·Leukemia & Lymphoma·Elena Díaz-Rodríguez, Atanasio Pandiella
Jan 9, 2014·Expert Review of Anticancer Therapy·Kim C Chan Chung, Rodger E Tiedemann
Oct 1, 2014·Expert Review of Hematology·Guillemette FouquetXavier Leleu
Apr 18, 2014·Expert Review of Anticancer Therapy·Massimo OffidaniAntonio Palumbo
May 8, 2015·Expert Review of Anticancer Therapy·Junya KurodaMasafumi Taniwaki
May 9, 2015·Expert Review of Hematology·Alan P Skarbnik, Andre H Goy
Apr 8, 2014·Expert Review of Clinical Pharmacology·Sowmya VaradaAlice B Gottlieb
Jun 19, 2013·Expert Opinion on Biological Therapy·Sonia Vallet, Klaus Podar
Aug 28, 2012·Expert Opinion on Emerging Drugs·Massimo GentileFortunato Morabito
Sep 24, 2015·International Journal of Oncology·Yen Ta HuangPei Chun Lai
Jan 6, 2016·Journal of Medicinal Chemistry·Iuliia BoichenkoBirte Hernandez Alvarez
Jul 29, 2016·Oncoimmunology·Isabelle KrämerMichael Hundemer

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
electrophoresis
ubiquitination
transfection
reverse transcription-PCR
enzyme-linked immunosorbent assay
thermal melt shift
thermal melt
dissection

Software Mentioned

GraFit

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.