Proteomic and protein interaction network analysis of human T lymphocytes during cell-cycle entry

Abstract

• The authors conduct a proteomic and protein interaction network analysis of human T lymphocytes during entry into the first cell cycle.

• Inhibiting the induction of eIF6 (60S ribosome biogenesis) causes T cells to enter the cell cycle without growing in size.

• Inhibiting the induction of SF3B2/SF3B4 (U2/U12-dependent RNA splicing) allows an increase in cell size without entering the cell cycle.

• These results provide proof of principle that blastogenesis and proliferation programs are separable in primary human T cells.

Abstract

Regulating the transition of cells such as T lymphocytes from quiescence (G ₀) into an activated, proliferating state involves initiation of cellular programs resulting in entry into the cell cycle (proliferation), the growth cycle (blastogenesis, cell size) and effector (functional) activation. We show the first proteomic analysis of protein interaction networks activated during entry into the first cell cycle from G ₀. We also provide proof of principle that blastogenesis and proliferation programs are separable in primary human T cells. We employed a proteomic profiling method to identify large-scale changes in chromatin/nuclear matrix-bound and unbound proteins in human T lymphocytes during the transition from G ₀ into the first cell cycle and mapped them to form functionally annotated, dynamic protein interaction networks. Inhibiting the induction of two proteins involved in two of the most significantly upregulated cellular processes, ribosome biogenesis (eIF6) and hnRNA splicing (SF3B2/SF3B4), showed, respectively, that human T cells can enter the cell cycle without growing in size, or increase in size without entering the cell cycle.