NDLI: Structural mechanisms of DREAM complex assembly and regulation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Guiley, Keelan Z. Liban, Tyler J. Felthousen, Jessica G. Ramanan, Parameshwaran Litovchick, Larisa Rubin, Seth M.
Description	Author Affiliation: Guiley KZ ( Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA); Liban TJ ( Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA); Felthousen JG ( Division of Hematology, Oncology, and Palliative Care, Richmond, Virginia 23298, USA); Ramanan P ( Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA); Litovchick L ( Division of Hematology, Oncology, and Palliative Care, Richmond, Virginia 23298, USA); Rubin SM ( Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA)
Abstract	The DREAM complex represses cell cycle genes during quiescence through scaffolding MuvB proteins with E2F4/5 and the Rb tumor suppressor paralog p107 or p130. Upon cell cycle entry, MuvB dissociates from p107/p130 and recruits B-Myb and FoxM1 for up-regulating mitotic gene expression. To understand the biochemical mechanisms underpinning DREAM function and regulation, we investigated the structural basis for DREAM assembly. We identified a sequence in the MuvB component LIN52 that binds directly to the pocket domains of p107 and p130 when phosphorylated on the DYRK1A kinase site S28. A crystal structure of the LIN52-p107 complex reveals that LIN52 uses a suboptimal LxSxExL sequence together with the phosphate at nearby S28 to bind the LxCxE cleft of the pocket domain with high affinity. The structure explains the specificity for p107/p130 over Rb in the DREAM complex and how the complex is disrupted by viral oncoproteins. Based on insights from the structure, we addressed how DREAM is disassembled upon cell cycle entry. We found that p130 and B-Myb can both bind the core MuvB complex simultaneously but that cyclin-dependent kinase phosphorylation of p130 weakens its association. Together, our data inform a novel target interface for studying MuvB and p130 function and the design of inhibitors that prevent tumor escape in quiescence.
File Format	HTM / HTML
ISSN	08909369
e-ISSN	15495477
DOI	10.1101/gad.257568.114
Journal	Genes & Development
Issue Number	9
Volume Number	29
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2015-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Cell Cycle Genetics Gene Expression Regulation Multiprotein Complexes Chemistry Metabolism Cell Cycle Proteins Crystallization Phosphorylation Protein Binding Protein Structure, Tertiary Retinoblastoma-like Protein P107 Retinoblastoma-like Protein P130 Sequence Alignment Trans-activators Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Genetics Developmental Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly.

Retinoblastoma protein (pRb), but not p107 or p130, is required for maintenance of enterocyte quiescence and differentiation in small intestine.

Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling.

Regulation of ischemic neuronal death by E2F4-p130 protein complexes.

Epigenetic control of mammalian LINE-1 retrotransposon by retinoblastoma proteins.

Combinatorial roles for pRB, p107, and p130 in E2F-mediated cell cycle control.

Sweet DREAMs for Hippo.

Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth.

Phosphorylation puts the pRb tumor suppressor into shape.

Structural mechanisms of DREAM complex assembly and regulation.

Similar Documents

DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly.

Retinoblastoma protein (pRb), but not p107 or p130, is required for maintenance of enterocyte quiescence and differentiation in small intestine.

Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling.

Regulation of ischemic neuronal death by E2F4-p130 protein complexes.

Epigenetic control of mammalian LINE-1 retrotransposon by retinoblastoma proteins.

Combinatorial roles for pRB, p107, and p130 in E2F-mediated cell cycle control.

Sweet DREAMs for Hippo.

Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth.

Phosphorylation puts the pRb tumor suppressor into shape.

Structural mechanisms of DREAM complex assembly and regulation.