Warning: The NCBI web site requires JavaScript to function. more...

My NCBI Sign In

Result Filters

Mol Cell Biol. 1998 Feb;18(2):753-61.

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

Lundberg AS, Weinberg RA.

Source

The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. Lundberg@wi.mit.edu

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.

PMID:: 9447971; [PubMed - indexed for MEDLINE]
PMCID:: PMC108786

Free PMC Article

Images from this publication.See all images (6) Free text

FIG. 1

FIG. 3

FIG. 5

FIG. 2

FIG. 4

FIG. 6

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

K11-CA69242/CA/NCI NIH HHS/United States

LinkOut - more resources

Full Text Sources

Other Literature Sources

Labome Researcher Resource - ExactAntigen/Labome

Supplemental Content

Icon for HighWire Press

Icon for PubMed Central

Save items

loading

Related citations in PubMed

Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo. [Mol Cell Biol. 2001]
Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo.
Ezhevsky SA, Ho A, Becker-Hapak M, Davis PK, Dowdy SF. Mol Cell Biol. 2001 Jul; 21(14):4773-84.
Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D:Cdk4/6 complexes results in active pRb. [Proc Natl Acad Sci U S A. 1997]
Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D:Cdk4/6 complexes results in active pRb.
Ezhevsky SA, Nagahara H, Vocero-Akbani AM, Gius DR, Wei MC, Dowdy SF. Proc Natl Acad Sci U S A. 1997 Sep 30; 94(20):10699-704.
The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. [EMBO J. 1996]
The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2.
Kitagawa M, Higashi H, Jung HK, Suzuki-Takahashi I, Ikeda M, Tamai K, Kato J, Segawa K, Yoshida E, Nishimura S, et al. EMBO J. 1996 Dec 16; 15(24):7060-9.
Review Induction of S phase by G1 regulatory factors. [Front Biosci. 1999]
Review Induction of S phase by G1 regulatory factors.
Kato J. Front Biosci. 1999 Dec 1; 4:D787-92. Epub 1999 Dec 1.
Review [Molecular mechanisms controlling the cell cycle: fundamental aspects and implications for oncology]. [Cancer Radiother. 2001]
Review [Molecular mechanisms controlling the cell cycle: fundamental aspects and implications for oncology].
Viallard JF, Lacombe F, Belloc F, Pellegrin JL, Reiffers J. Cancer Radiother. 2001 Apr; 5(2):109-29.

See reviews... See all...

Cited by over 100 PubMed Central articles

Strategic cell-cycle regulatory features that provide Mammalian cells with tunable g1 length and reversible g1 arrest. [PLoS One. 2012]
Strategic cell-cycle regulatory features that provide Mammalian cells with tunable g1 length and reversible g1 arrest.
Pfeuty B. PLoS One. 2012; 7(4):e35291. Epub 2012 Apr 23.
The retinoblastoma family of proteins and their regulatory functions in the mammalian cell division cycle. [Cell Div. 2012]
The retinoblastoma family of proteins and their regulatory functions in the mammalian cell division cycle.
Henley SA, Dick FA. Cell Div. 2012 Mar 14; 7(1):10. Epub 2012 Mar 14.
MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1. [PLoS One. 2012]
MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1.
Zhang W, Kong G, Zhang J, Wang T, Ye L, Zhang X. PLoS One. 2012; 7(2):e31450. Epub 2012 Feb 3.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
References for this PMC Article
Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Free in PMC
Free full text articles in PMC
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Functional inactivation of the retinoblastoma protein requires sequential modifi...
Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes.
Mol Cell Biol. 1998 Feb ;18(2):753-61.

PubMed
Aprotinin decreases blood loss and homologous transfusions in patients undergoin...
Aprotinin decreases blood loss and homologous transfusions in patients undergoing major orthopedic surgery.
Anesthesiology. 1998 Jan ;88(1):50-7.

PubMed
Prostaglandin-macromolecule interactions. I. Noncovalent binding of prostaglandi...
Prostaglandin-macromolecule interactions. I. Noncovalent binding of prostaglandins A1, E1, F2alpha, and E2 by human and bovine serum albumins.
J Pharmacol Exp Ther. 1976 May ;197(2):391-401.

PubMed
Immunocytochemical localization of GABA, GABAA receptors, and synapse-associated...
Immunocytochemical localization of GABA, GABAA receptors, and synapse-associated proteins in the developing and adult ferret retina.
Vis Neurosci. 1997 Nov-Dec ;14(6):1097-108.

PubMed
How people get into mental health services: stories of choice, coercion and "mud...
How people get into mental health services: stories of choice, coercion and "muddling through" from "first-timers".
Soc Sci Med. 1998 Jan ;46(2):275-86.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

You are here: NCBI > Literature > PubMed

Write to the Help Desk