cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines

Pedro Rodriguez-Collazo, Sara K. Snyder, Rebecca C. Chiffer, Jordanka Zlatanova, Sanford H. Leuba, Catharine Smith

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The phosphorylation of histone H3 is known to play a role in regulation of transcription as well as preparation of chromosomes for mitosis. Various signaling cascades induce H3 phosphorylation, particularly at genes activated by these pathways. In this study, we show that signaling can also have the opposite effect. Activators of cAMP signaling induce a rapid and potent loss of H3 phosphorylation. This effect is not mediated through a cAMP metabolite since a membrane-permeable form of AMP had no effect on H3 phosphorylation and a phosphodiesterase-resistant cAMP analog efficiently reduced it. cAMP is also the likely regulator of H3 phosphorylation under physiological conditions since only supra-pharmacological doses of cGMP induce the loss of H3 phosphorylation. The loss of phosphorylation is specific for histone H3 since we do not observe drastic losses in total phosphorylation of other histones. In addition, other H3 modifications are unaffected with the exception of lysine 9 methylation, which is elevated. Analysis of cell growth and cell cycle shows that cAMP signaling inhibits cell growth and arrests cells at both G1 and G2/M. Similar effects of cAMP signaling on H3 phosphorylation are observed in a variety of mammary adenocarcinoma-derived cell lines. In syngeneic human breast-derived cell lines, one diploid and non-transformed, the other derived from a ductal carcinoma, the loss of H3 phosphorylation is significantly more sensitive to cAMP concentration in the transformed cell line.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalExperimental Cell Research
Volume314
Issue number1
DOIs
StatePublished - Jan 1 2008

Fingerprint

Histones
Adenocarcinoma
Breast
Phosphorylation
Cell Line
Ductal Carcinoma
Transformed Cell Line
Phosphoric Diester Hydrolases
Adenosine Monophosphate
Growth
Diploidy
Mitosis
Methylation
Lysine
Cell Cycle
Chromosomes
Pharmacology
Membranes

Keywords

  • cAMP signaling
  • Cell cycle
  • Chromatin
  • Histone H3
  • Phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines. / Rodriguez-Collazo, Pedro; Snyder, Sara K.; Chiffer, Rebecca C.; Zlatanova, Jordanka; Leuba, Sanford H.; Smith, Catharine.

In: Experimental Cell Research, Vol. 314, No. 1, 01.01.2008, p. 1-10.

Research output: Contribution to journalArticle

Rodriguez-Collazo, Pedro ; Snyder, Sara K. ; Chiffer, Rebecca C. ; Zlatanova, Jordanka ; Leuba, Sanford H. ; Smith, Catharine. / cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines. In: Experimental Cell Research. 2008 ; Vol. 314, No. 1. pp. 1-10.
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