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Title: Structural mechanism of Myb–MuvB assembly

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. Here, 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.

Authors:
 [1];  [2];  [2]; ORCiD logo [1];  [3];  [2];  [1]
  1. Univ. of California, Santa Cruz, CA (United States)
  2. Virginia Commonwealth Univ., Richmond, VA (United States)
  3. Stanford Univ., CA (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1478077
Grant/Contract Number:  
F31CA206244; R01CA128836; R01CA188571; R01CA132685; R01GM124148
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 115; Journal Issue: 40; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; cell cycle; transcription factor; Myb; MuvB; DREAM

Citation Formats

Guiley, Keelan Z., Iness, Audra N., Saini, Siddharth, Tripathi, Sarvind, Lipsick, Joseph S., Litovchick, Larisa, and Rubin, Seth M. Structural mechanism of Myb–MuvB assembly. United States: N. p., 2018. Web. doi:10.1073/pnas.1808136115.
Guiley, Keelan Z., Iness, Audra N., Saini, Siddharth, Tripathi, Sarvind, Lipsick, Joseph S., Litovchick, Larisa, & Rubin, Seth M. Structural mechanism of Myb–MuvB assembly. United States. doi:10.1073/pnas.1808136115.
Guiley, Keelan Z., Iness, Audra N., Saini, Siddharth, Tripathi, Sarvind, Lipsick, Joseph S., Litovchick, Larisa, and Rubin, Seth M. Mon . "Structural mechanism of Myb–MuvB assembly". United States. doi:10.1073/pnas.1808136115. https://www.osti.gov/servlets/purl/1478077.
@article{osti_1478077,
title = {Structural mechanism of Myb–MuvB assembly},
author = {Guiley, Keelan Z. and Iness, Audra N. and Saini, Siddharth and Tripathi, Sarvind and Lipsick, Joseph S. and Litovchick, Larisa and Rubin, Seth M.},
abstractNote = {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. Here, 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.},
doi = {10.1073/pnas.1808136115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 40,
volume = 115,
place = {United States},
year = {2018},
month = {9}
}

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Cited by: 4 works
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