Abstract

A stable transformed fibrosarcoma cell line has been derived containing the C/EBP-alpha gene under control of the lac repressor. Preliminary studies have demonstrated that C/EBP-alpha expression leads to growth arrest and increased expression of p21/WAF1/SDI1. The latter is an important negative regulator of cell proliferation. Also, co-immunoprecipitation has demonstrated direct binding of C/EBP-alpha to p21.
In Aim I, a two hybrid expression system will be used to determine whether this binding occurs in vivo. Then, to further define cellular pathways that regulate interaction of the two proteins, a subtraction cDNA library will be constructed, enriched for genes differentially activated by C/EBP-alpha. This library will be the source of genes that can be tested for their ability to alter p21 expression.
In Aim II, liver regeneration will be studied in the p21 knock-out mouse. Finally, Aim III studies will investigate liver regeneration in old rats, which have altered regulation of both C/EBP-alpha and p21.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055188-02
Application #
2771075
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1997-09-01
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Jin, Jingling; Hong, Il-Hwa; Lewis, Kyle et al. (2015) Cooperation of C/EBP family proteins and chromatin remodeling proteins is essential for termination of liver regeneration. Hepatology 61:315-25
Jin, Jingling; Iakova, Polina; Breaux, Meghan et al. (2013) Increased expression of enzymes of triglyceride synthesis is essential for the development of hepatic steatosis. Cell Rep 3:831-43
Jiang, Yanjun; Jin, Jingling; Iakova, Polina et al. (2013) Farnesoid X receptor directly regulates xenobiotic detoxification genes in the long-lived Little mice. Mech Ageing Dev 134:407-15
Jiang, Yanjun; Iakova, Polina; Jin, Jingling et al. (2013) Farnesoid X receptor inhibits gankyrin in mouse livers and prevents development of liver cancer. Hepatology 57:1098-106
Jones, Karlie; Timchenko, Lubov; Timchenko, Nikolai A (2012) The role of CUGBP1 in age-dependent changes of liver functions. Ageing Res Rev 11:442-9
Jin, Jingling; Iakova, Polina; Jiang, Yanjun et al. (2011) The reduction of SIRT1 in livers of old mice leads to impaired body homeostasis and to inhibition of liver proliferation. Hepatology 54:989-98
Jones, Karlie; Jin, Bingwen; Iakova, Polina et al. (2011) RNA Foci, CUGBP1, and ZNF9 are the primary targets of the mutant CUG and CCUG repeats expanded in myotonic dystrophies type 1 and type 2. Am J Pathol 179:2475-89
Haefliger, Simon; Klebig, Christiane; Schaubitzer, Kerstin et al. (2011) Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML. Blood 117:5931-40
Iakova, Polina; Timchenko, Lubov; Timchenko, Nikolai A (2011) Intracellular signaling and hepatocellular carcinoma. Semin Cancer Biol 21:28-34
Jin, Jingling; Wang, Guo-Li; Iakova, Polina et al. (2010) Epigenetic changes play critical role in age-associated dysfunctions of the liver. Aging Cell 9:895-910

Showing the most recent 10 out of 19 publications