Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes.

Molecular and Cellular Biology
A S Lundberg, R A Weinberg

Abstract

The retinoblastoma protein (pRb) acts to constrain the G1-S transition in mammalian cells. Phosphorylation of pRb in G1 inactivates its growth-inhibitory function, allowing for cell cycle progression. Although several cyclins and associated cyclin-dependent kinases (cdks) have been implicated in pRb phosphorylation, the precise mechanism by which pRb is phosphorylated in vivo remains unclear. By inhibiting selectively either cdk4/6 or cdk2, we show that endogenous D-type cyclins, acting with cdk4/6, are able to phosphorylate pRb only partially, a process that is likely to be completed by cyclin E-cdk2 complexes. Furthermore, cyclin E-cdk2 is unable to phosphorylate pRb in the absence of prior phosphorylation by cyclin D-cdk4/6 complexes. Complete phosphorylation of pRb, inactivation of E2F binding, and activation of E2F transcription occur only after sequential action of at least two distinct G1 cyclin kinase complexes.

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J A DeCaprioD M Livingston
Apr 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D J TempletonR A Weinberg
Oct 16, 1989·Biochemical and Biophysical Research Communications·Y TayaS Nishimura
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·R H MedemaR A Weinberg
May 1, 1995·Molecular and Cellular Biology·M OhtsuboM Pagano
Nov 18, 1994·Cell·C J Sherr
Aug 1, 1994·Genes & Development·B D DynlachtE Harlow
Mar 1, 1994·Molecular and Cellular Biology·M Meyerson, E Harlow
Dec 24, 1993·Science·S van den Heuvel, E Harlow
Apr 5, 1996·The Journal of Biological Chemistry·E S Knudsen, J Y Wang
Apr 1, 1996·Molecular and Cellular Biology·K MobergJ A Lees
Jul 1, 1996·Molecular and Cellular Biology·C L WuE Harlow
Jan 1, 1997·Molecular and Cellular Biology·K Zerfass-ThomeP Jansen-Dürr
Apr 11, 1997·The Journal of Biological Chemistry·X TanJ Y Wang
May 9, 1997·The Journal of Biological Chemistry·T Zarkowska, S Mittnacht

❮ Previous
Next ❯

Citations

Jun 19, 2004·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·D AtallahJ-M Renoir
Jan 6, 2006·Growth Factors·Elizabeth A Musgrove
Dec 27, 2013·Expert Opinion on Pharmacotherapy·Andrea RoccaDino Amadori
Mar 4, 2014·Expert Opinion on Pharmacotherapy·Eilin AustreidHans Petter Eikesdal
Dec 17, 2014·Expert Opinion on Investigational Drugs·Jeffrey D Altenburg, Sherif S Farag
Apr 1, 2007·Expert Opinion on Drug Discovery·Timothy A YapS de Bono
Jun 8, 1999·The Journal of Experimental Medicine·D A TanguayT L Rothstein
Dec 12, 2012·Trends in Biochemical Sciences·Seth M Rubin
Oct 10, 2002·Kidney International·Baolian Liu, Patricia A Preisig
May 1, 2012·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Haviryaji S G Kalluri, Robert J Dempsey
Dec 21, 2011·Biochemical and Biophysical Research Communications·Bo WangNaoyuki Miura
Aug 28, 2003·Cell·Yan GengPiotr Sicinski
Feb 5, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yong-qiang HuaLu-ming Liu
Nov 13, 2010·Toxicology and Applied Pharmacology·Jianling WangM Firoze Khan
Mar 5, 2016·In Vitro Cellular & Developmental Biology. Animal·Ying ZhangYundai Chen
Aug 17, 2010·Biochimica Et Biophysica Acta·Sunil Kumar MaloniaSamit Chattopadhyay
May 21, 2010·Cancer Letters·Yun MengDaiming Fan
Mar 20, 2010·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Yang LiuLuciana L Almada
Jun 15, 2011·Journal of Neuropathology and Experimental Neurology·Jeremy G StoneHyoung-gon Lee
Jun 10, 2009·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Kyohei AgoMakoto Shibutani
Dec 17, 2008·Biochemical and Biophysical Research Communications·Dong Wan ChooSang Soo Kim
Nov 26, 2008·Experimental Cell Research·Michelle N YarmoAlexander Sorisky
Nov 13, 2008·Journal of Bioscience and Bioengineering·Yoshihiko TashimaTaizo Hanai
Jul 26, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yong Hwan HanWoo Hyun Park
Jul 10, 2007·Blood Cells, Molecules & Diseases·Mark PilkintonOscar R Colamonici
Jan 8, 2008·Biophysical Journal·Azi LipshtatAvi Ma'ayan
Sep 1, 2015·Cell Cycle·Solomon TadesseShudong Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.