When in the nucleus, ERK1/2 dislodges the retinoblastoma protein from lamin A, facilitating its rapid phosphorylation

Ajenjo

Andrés

Arozarena

Balmanno

Berta Casar

Boban

Broers

Camps

Casar

Chambard

Cheng

Cohen-Armon

Daksis

Dorner

D’Abaco

Fernando Calvo

Foster

Gille

González

Ivorra

Javier Rodríguez

Johnson

Jones

José M. González

Keenan

Kenworthy

Kerkhoff

Krek

Lavoie

Lenormand

Malumbres

Mancini

Markiewicz

Matallanas

Naetar

Nitta

Ottaviani

Ozaki

Pekovic

Piero Crespo

Raman

Santamaría

Sanz-Moreno

Schneider

Seth

Shapiro

Shimi

Soule

Sullivan

Van Berlo

Vicente Andrés

Villanueva

Vlcek

Weber

Weinberg

Weintraub

Wolf

Yamamoto

Zalvide

The Journal of Cell Biology

English

PubMed

As orchestrators of essential cellular processes like proliferation, ERK1/2 mitogen-activated protein kinase signals impact on cell cycle regulation. A-type lamins are major constituents of the nuclear matrix that also control the cell cycle machinery by largely unknown mechanisms. In this paper, we disclose a functional liaison between ERK1/2 and lamin A whereby cell cycle progression is regulated. We demonstrate that lamin A serves as a mutually exclusive dock for ERK1/2 and the retinoblastoma (Rb) protein. Our results reveal that, immediately after their postactivation entrance in the nucleus, ERK1/2 dislodge Rb from its interaction with lamin A, thereby facilitating its rapid phosphorylation and consequently promoting E2F activation and cell cycle entry. Interestingly, these effects are independent of ERK1/2 kinase activity. We also show that cellular transformation and tumor cell proliferation are dependent on the balance between lamin A and nuclear ERK1/2 levels, which determines Rb accessibility for phosphorylation/inactivation

Rodríguez Martínez, Javier

Calvo González, Fernando

Casar Martínez, Berta

Crespo, Piero

UCrea

ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma-lamin A complexes

González Granado, José María

Andrés García, Vicente

Crespo Baraja, Piero

Crossref

ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma–lamin A complexes

As orchestrators of essential cellular processes like proliferation, ERK1/2 mitogen-activated protein kinase signals impact on cell cycle regulation. A-type lamins are major constituents of the nuclear matrix that also control the cell cycle machinery by largely unknown mechanisms. In this paper, we disclose a functional liaison between ERK1/2 and lamin A whereby cell cycle progression is regulated. We demonstrate that lamin A serves as a mutually exclusive dock for ERK1/2 and the retinoblastoma (Rb) protein. Our results reveal that, immediately after their postactivation entrance in the nucleus, ERK1/2 dislodge Rb from its interaction with lamin A, thereby facilitating its rapid phosphorylation and consequently promoting E2F activation and cell cycle entry. Interestingly, these effects are independent of ERK1/2 kinase activity. We also show that cellular transformation and tumor cell proliferation are dependent on the balance between lamin A and nuclear ERK1/2 levels, which determines Rb accessibility for phosphorylation/inactivation.</jats:p

As orchestrators of essential cellular processes like proliferation, ERK1/2 mitogen-activated protein kinase signals impact on cell cycle regulation. A-type lamins are major constituents of the nuclear matrix that also control the cell cycle machinery by largely unknown mechanisms. In this paper, we disclose a functional liaison between ERK1/2 and lamin A whereby cell cycle progression is regulated. We demonstrate that lamin A serves as a mutually exclusive dock for ERK1/2 and the retinoblastoma (Rb) protein. Our results reveal that, immediately after their postactivation entrance in the nucleus, ERK1/2 dislodge Rb from its interaction with lamin A, thereby facilitating its rapid phosphorylation and consequently promoting E2F activation and cell cycle entry. Interestingly, these effects are independent of ERK1/2 kinase activity. We also show that cellular transformation and tumor cell proliferation are dependent on the balance between lamin A and nuclear ERK1/2 levels, which determines Rb accessibility for phosphorylation/inactivation.P. Crespo’s laboratory is supported by grants from the Spanish Ministry of Science and Innovation (BFU2008-01728), the GROWTHSTOP project from the European Union VI Framework Program (LSHC-CT-2006-037731), and the
Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0105),
Spanish Ministry of Health. V. Andrés’s laboratory is supported by the Spanish
Ministry of Science and Innovation (SAF2007-62110), the European Regional
Development Fund, and the Red Temática de Investigación Cooperativa en
Enfermedades Cardiovasculares (RD06/0014/0021). The Centro Nacional de Investigaciones Cardiovasculares is supported by the Spanish Ministry of Science and Innovation and the Fundación Pro–Centro Nacional de Investigaciones
Cardiovasculares.Peer reviewe

Rodríguez, Javier

Calvo, Fernando

González, José M.

Casar, Berta

Andrés, Vicente

Digital.CSIC

A- and B-type lamins are differentially expressed in normal human tissues.

and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev.

Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase.

Extracellular signal-regulated kinase activates topoisomerase IIalpha through a mechanism independent of phosphorylation.

Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res.

Lamina-associated polypeptide 2 regulates cell cycle progression and differentiation via the retinoblastoma– E2F pathway.

Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy.

Mxi2 promotes stimulusindependent ERK nuclear translocation.

Myeloid leukemia cell growth and differentiation are independent of mitogen-activated protein kinase ERK1/2 activation.

Nucleoplasmic LAP2–lamin A complexes are required to maintain a proliferative state in human fibroblasts.

the activation loop of ERK in the detachment from cytosolic anchoring.

The retinoblastoma protein and cell cycle control.

The Rho family GTPase Cdc42 regulates the activation of Ras/MAP kinase by the exchange factor Ras-GRF.

http://jcb.rupress.org/content/jcb/191/5/967.full.pdf

ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma–lamin A complexes

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