Myc stimulates B lymphocyte differentiation and amplifies calcium signaling

Tania Habib, Heon Park, Mark Tsang, Ignacio Moreno De Alborán, Andrea Nicks, Leslie Wilson, Paul S Knoepfler, Sarah Andrews, David J. Rawlings, Robert N. Eisenman, Brian M. Iritani

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Deregulated expression of the Myc family of transcription factors (c-, N-, and L-myc) contributes to the development of many cancers by a mechanism believed to involve the stimulation of cell proliferation and inhibition of differentiation. However, using B cell-specific c-/N-myc double-knockout mice and Eμ-myc transgenic mice bred onto genetic backgrounds (recombinase- activating gene 2-/- and Btk-/- Tec-/-) whereby B cell development is arrested, we show that Myc is necessary to stimulate both proliferation and differentiation in primary B cells. Moreover, Myc expression results in sustained increases in intracellular Ca2+ ([Ca 2+]i), which is required for Myc to stimulate B cell proliferation and differentiation. The increase in [Ca2+]i correlates with constitutive nuclear factor of activated T cells (NFAT) nuclear translocation, reduced Ca2+ efflux, and decreased expression of the plasma membrane Ca2+-adenosine triphosphatase (PMCA) efflux pump. Our findings demonstrate a revised model whereby Myc promotes both proliferation and differentiation, in part by a remarkable mechanism whereby Myc amplifies Ca2+ signals, thereby enabling the concurrent expression of Myc- and Ca2+-regulated target genes.

Original languageEnglish (US)
Pages (from-to)717-731
Number of pages15
JournalJournal of Cell Biology
Volume179
Issue number4
DOIs
StatePublished - Nov 19 2007
Externally publishedYes

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Calcium Signaling
B-Lymphocytes
Cell Proliferation
NFATC Transcription Factors
Recombinases
Knockout Mice
Transgenic Mice
Genes
Adenosine Triphosphatases
Cell Differentiation
Transcription Factors
Cell Membrane
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

Habib, T., Park, H., Tsang, M., De Alborán, I. M., Nicks, A., Wilson, L., ... Iritani, B. M. (2007). Myc stimulates B lymphocyte differentiation and amplifies calcium signaling. Journal of Cell Biology, 179(4), 717-731. https://doi.org/10.1083/jcb.200704173

Myc stimulates B lymphocyte differentiation and amplifies calcium signaling. / Habib, Tania; Park, Heon; Tsang, Mark; De Alborán, Ignacio Moreno; Nicks, Andrea; Wilson, Leslie; Knoepfler, Paul S; Andrews, Sarah; Rawlings, David J.; Eisenman, Robert N.; Iritani, Brian M.

In: Journal of Cell Biology, Vol. 179, No. 4, 19.11.2007, p. 717-731.

Research output: Contribution to journalArticle

Habib, T, Park, H, Tsang, M, De Alborán, IM, Nicks, A, Wilson, L, Knoepfler, PS, Andrews, S, Rawlings, DJ, Eisenman, RN & Iritani, BM 2007, 'Myc stimulates B lymphocyte differentiation and amplifies calcium signaling', Journal of Cell Biology, vol. 179, no. 4, pp. 717-731. https://doi.org/10.1083/jcb.200704173
Habib T, Park H, Tsang M, De Alborán IM, Nicks A, Wilson L et al. Myc stimulates B lymphocyte differentiation and amplifies calcium signaling. Journal of Cell Biology. 2007 Nov 19;179(4):717-731. https://doi.org/10.1083/jcb.200704173
Habib, Tania ; Park, Heon ; Tsang, Mark ; De Alborán, Ignacio Moreno ; Nicks, Andrea ; Wilson, Leslie ; Knoepfler, Paul S ; Andrews, Sarah ; Rawlings, David J. ; Eisenman, Robert N. ; Iritani, Brian M. / Myc stimulates B lymphocyte differentiation and amplifies calcium signaling. In: Journal of Cell Biology. 2007 ; Vol. 179, No. 4. pp. 717-731.
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