Abstract
The MuvB transcriptional regulatory complex, which controls cell-cycle-dependent gene expression, cooperates with B-Myb to activate genes required for the G2 and M phases of the cell cycle. We have identified the domain in B-Myb that is essential for the assembly of the Myb-MuvB (MMB) complex. We determined a crystal structure that reveals how this B-Myb domain binds MuvB through the adaptor protein LIN52 and the scaffold protein LIN9. The structure and biochemical analysis provide an understanding of how oncogenic B-Myb is recruited to regulate genes required for cell-cycle progression, and the MMB interface presents a potential therapeutic target to inhibit cancer cell proliferation.
Keywords:
DREAM; MuvB; Myb; cell cycle; transcription factor.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cell Cycle Proteins* / chemistry
-
Cell Cycle Proteins* / metabolism
-
Cell Cycle*
-
Cell Line
-
Crystallography, X-Ray
-
Humans
-
Multiprotein Complexes* / chemistry
-
Multiprotein Complexes* / metabolism
-
Neoplasm Proteins* / chemistry
-
Neoplasm Proteins* / metabolism
-
Neoplasms* / chemistry
-
Neoplasms* / metabolism
-
Nuclear Proteins* / chemistry
-
Nuclear Proteins* / metabolism
-
Protein Domains
-
Trans-Activators* / chemistry
-
Trans-Activators* / metabolism
-
Tumor Suppressor Proteins* / chemistry
-
Tumor Suppressor Proteins* / metabolism
Substances
-
Cell Cycle Proteins
-
LIN9 protein, human
-
MYBL2 protein, human
-
Multiprotein Complexes
-
Neoplasm Proteins
-
Nuclear Proteins
-
Trans-Activators
-
Tumor Suppressor Proteins