6dbp

From Proteopedia

RNA-recognition motif 1 of human MSI2

PDB ID 6dbp

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Structural highlights

6dbp is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.603Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MSI2H_HUMAN Chromosomal aberrations involving MSI2 may contribute to disease progression in chronic myeloid leukemia. Translocation t(7;17)(p15;q23) with HOXA9; translocation t(7;17)(q32-34;q23).^[1]

Function

MSI2H_HUMAN RNA binding protein that regulates the expression of target mRNAs at the translation level. May play a role in the proliferation and maintenance of stem cells in the central nervous system (By similarity).

Publication Abstract from PubMed

The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI's oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.

Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia.,Minuesa G, Albanese SK, Xie W, Kazansky Y, Worroll D, Chow A, Schurer A, Park SM, Rotsides CZ, Taggart J, Rizzi A, Naden LN, Chou T, Gourkanti S, Cappel D, Passarelli MC, Fairchild L, Adura C, Glickman JF, Schulman J, Famulare C, Patel M, Eibl JK, Ross GM, Bhattacharya S, Tan DS, Leslie CS, Beuming T, Patel DJ, Goldgur Y, Chodera JD, Kharas MG Nat Commun. 2019 Jun 19;10(1):2691. doi: 10.1038/s41467-019-10523-3. PMID:31217428^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Barbouti A, Hoglund M, Johansson B, Lassen C, Nilsson PG, Hagemeijer A, Mitelman F, Fioretos T. A novel gene, MSI2, encoding a putative RNA-binding protein is recurrently rearranged at disease progression of chronic myeloid leukemia and forms a fusion gene with HOXA9 as a result of the cryptic t(7;17)(p15;q23). Cancer Res. 2003 Mar 15;63(6):1202-6. PMID:12649177
↑ Minuesa G, Albanese SK, Xie W, Kazansky Y, Worroll D, Chow A, Schurer A, Park SM, Rotsides CZ, Taggart J, Rizzi A, Naden LN, Chou T, Gourkanti S, Cappel D, Passarelli MC, Fairchild L, Adura C, Glickman JF, Schulman J, Famulare C, Patel M, Eibl JK, Ross GM, Bhattacharya S, Tan DS, Leslie CS, Beuming T, Patel DJ, Goldgur Y, Chodera JD, Kharas MG. Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia. Nat Commun. 2019 Jun 19;10(1):2691. doi: 10.1038/s41467-019-10523-3. PMID:31217428 doi:http://dx.doi.org/10.1038/s41467-019-10523-3