Regulation of apoptotic and growth inhibitory activities of C/EBP{alpha} in different cell lines

Journal Article · Tue Apr 15 04:00:00 EDT 2008 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2008.01.028· OSTI ID:21128173

Guoli, Wang ^[1]; Xiurong, Shi; Salisbury, Elizabeth ^[2]; Timchenko, Nikolai A ^[1]

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1. Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030 (United States)
2. Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030 (United States)

C/EBP{alpha} is expressed in many tissues and inhibits cell growth. In this paper, we have examined mechanisms which regulate activities of C/EBP{alpha} in cell lines derived from different tissues. We found that C/EBP{alpha} possesses strong pro-apoptotic activity in NIH3T3 cells, while this activity is not detected in 3T3-L1, Hep3B2 and HEK293 cells. Micro-array data show that C/EBP{alpha} activates many genes of apoptosis signaling in NIH3T3 cells. One of these genes, ARL6IP5, is a direct target of C/EBP{alpha} and is a key mediator of the apoptosis. Using C/EBP{alpha} mutants which do not cause cell death; we have found that C/EBP{alpha} does not arrest proliferation of NIH3T3 cells. The lack of growth arrest in NIH3T3 cells correlates with the inhibition of p16INK4 and with low levels of cyclin D3. The limited growth inhibitory activity of C/EBP{alpha} is also observed in Hep3B2 cells which express low levels of cyclin D3. Elevation of cyclin D3 restores growth inhibitory activity of C/EBP{alpha} in NIH3T3 and in Hep3B2 cells. These data show that apoptotic and growth inhibitory activities of C/EBP{alpha} are differentially regulated in different cells and that cooperation of cyclin D3 and C/EBP{alpha} is required for the inhibition of proliferation.

• OSTI ID: 21128173
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 7 Vol. 314; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL GROWTH
APOPTOSIS
CELL PROLIFERATION
GENES
INHIBITION
MUTANTS