cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression

Pedro Rodriguez-Collazo; Sara K. Snyder; Rebecca C. Chiffer; Erin A. Bressler; Ty C. Voss; Eric P. Anderson; Hans Gottfried Genieser; Catharine L. Smith

doi:10.1016/j.yexcr.2008.06.022

cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression

Pedro Rodriguez-Collazo, Sara K. Snyder, Rebecca C. Chiffer, Erin A. Bressler, Ty C. Voss, Eric P. Anderson, Hans Gottfried Genieser, Catharine L. Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in quiescent cells but dramatically reducing it in cycling cells. The latter is due to a rapid and dramatic loss of mitotic histone H3 phosphorylation caused by a disruption in G2 progression, as evidenced by the inhibition of mitotic entry and decreased activity of the CyclinB/Cdk1 kinase. The inhibition of G2 progression induced through cAMP signaling is dependent on expression of the catalytic subunit of PKA and is highly sensitive to intracellular cAMP concentration. The mechanism by which G2 progression is inhibited is independent of both DNA damage and MAP kinase signaling. Our results suggest that cAMP signaling activates a G2 checkpoint by a unique mechanism and provide new insight into normal cellular regulation of G2 progression.

Original language	English (US)
Pages (from-to)	2855-2869
Number of pages	15
Journal	Experimental Cell Research
Volume	314
Issue number	15
DOIs	https://doi.org/10.1016/j.yexcr.2008.06.022
State	Published - Sep 10 2008
Externally published	Yes

Funding

We are grateful to members of the Laboratory of Receptor Biology and Gene Expression (NCI) for helpful discussion, to Barbara Taylor (NCI) at the Center for Cancer Research (CCR) FACS Core Facility for assistance with FACS analysis, and to Tatiana Karpova (NCI) and the CCR Core Fluorescence Imaging Facility for training and assistance with the confocal microscope. We also thank Drs. Carole Parent (NCI), Michael Bustin (NCI) and Ted Weinert (University of Arizona) for a critical reading of the manuscript. This project was supported in part through an Intramural Research Award (NCI) to CLS and NCI 1K01CA122177-01A1 to PRC.

Keywords

Cell cycle
Cyclin B
Cyclin-dependent kinase
Histone phosphorylation
Protein kinase A
cAMP signaling

ASJC Scopus subject areas

Cell Biology

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10.1016/j.yexcr.2008.06.022

Cite this

@article{b834151d1fdb443183fc388de65f590b,

title = "cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression",

abstract = "cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in quiescent cells but dramatically reducing it in cycling cells. The latter is due to a rapid and dramatic loss of mitotic histone H3 phosphorylation caused by a disruption in G2 progression, as evidenced by the inhibition of mitotic entry and decreased activity of the CyclinB/Cdk1 kinase. The inhibition of G2 progression induced through cAMP signaling is dependent on expression of the catalytic subunit of PKA and is highly sensitive to intracellular cAMP concentration. The mechanism by which G2 progression is inhibited is independent of both DNA damage and MAP kinase signaling. Our results suggest that cAMP signaling activates a G2 checkpoint by a unique mechanism and provide new insight into normal cellular regulation of G2 progression.",

keywords = "Cell cycle, Cyclin B, Cyclin-dependent kinase, Histone phosphorylation, Protein kinase A, cAMP signaling",

author = "Pedro Rodriguez-Collazo and Snyder, {Sara K.} and Chiffer, {Rebecca C.} and Bressler, {Erin A.} and Voss, {Ty C.} and Anderson, {Eric P.} and Genieser, {Hans Gottfried} and Smith, {Catharine L.}",

note = "Funding Information: We are grateful to members of the Laboratory of Receptor Biology and Gene Expression (NCI) for helpful discussion, to Barbara Taylor (NCI) at the Center for Cancer Research (CCR) FACS Core Facility for assistance with FACS analysis, and to Tatiana Karpova (NCI) and the CCR Core Fluorescence Imaging Facility for training and assistance with the confocal microscope. We also thank Drs. Carole Parent (NCI), Michael Bustin (NCI) and Ted Weinert (University of Arizona) for a critical reading of the manuscript. This project was supported in part through an Intramural Research Award (NCI) to CLS and NCI 1K01CA122177-01A1 to PRC.",

year = "2008",

month = sep,

day = "10",

doi = "10.1016/j.yexcr.2008.06.022",

language = "English (US)",

volume = "314",

pages = "2855--2869",

journal = "Experimental Cell Research",

issn = "0014-4827",

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TY - JOUR

T1 - cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression

AU - Rodriguez-Collazo, Pedro

AU - Snyder, Sara K.

AU - Chiffer, Rebecca C.

AU - Bressler, Erin A.

AU - Voss, Ty C.

AU - Anderson, Eric P.

AU - Genieser, Hans Gottfried

AU - Smith, Catharine L.

N1 - Funding Information: We are grateful to members of the Laboratory of Receptor Biology and Gene Expression (NCI) for helpful discussion, to Barbara Taylor (NCI) at the Center for Cancer Research (CCR) FACS Core Facility for assistance with FACS analysis, and to Tatiana Karpova (NCI) and the CCR Core Fluorescence Imaging Facility for training and assistance with the confocal microscope. We also thank Drs. Carole Parent (NCI), Michael Bustin (NCI) and Ted Weinert (University of Arizona) for a critical reading of the manuscript. This project was supported in part through an Intramural Research Award (NCI) to CLS and NCI 1K01CA122177-01A1 to PRC.

PY - 2008/9/10

Y1 - 2008/9/10

N2 - cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in quiescent cells but dramatically reducing it in cycling cells. The latter is due to a rapid and dramatic loss of mitotic histone H3 phosphorylation caused by a disruption in G2 progression, as evidenced by the inhibition of mitotic entry and decreased activity of the CyclinB/Cdk1 kinase. The inhibition of G2 progression induced through cAMP signaling is dependent on expression of the catalytic subunit of PKA and is highly sensitive to intracellular cAMP concentration. The mechanism by which G2 progression is inhibited is independent of both DNA damage and MAP kinase signaling. Our results suggest that cAMP signaling activates a G2 checkpoint by a unique mechanism and provide new insight into normal cellular regulation of G2 progression.

AB - cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in quiescent cells but dramatically reducing it in cycling cells. The latter is due to a rapid and dramatic loss of mitotic histone H3 phosphorylation caused by a disruption in G2 progression, as evidenced by the inhibition of mitotic entry and decreased activity of the CyclinB/Cdk1 kinase. The inhibition of G2 progression induced through cAMP signaling is dependent on expression of the catalytic subunit of PKA and is highly sensitive to intracellular cAMP concentration. The mechanism by which G2 progression is inhibited is independent of both DNA damage and MAP kinase signaling. Our results suggest that cAMP signaling activates a G2 checkpoint by a unique mechanism and provide new insight into normal cellular regulation of G2 progression.

KW - Cell cycle

KW - Cyclin B

KW - Cyclin-dependent kinase

KW - Histone phosphorylation

KW - Protein kinase A

KW - cAMP signaling

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DO - 10.1016/j.yexcr.2008.06.022

M3 - Article

C2 - 18644368

AN - SCOPUS:50049115247

SN - 0014-4827

VL - 314

SP - 2855

EP - 2869

JO - Experimental Cell Research

JF - Experimental Cell Research

IS - 15

ER -

cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression

Abstract

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Keywords

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