ABSTRACT
The E1A-targeted transcription factor E4F1 is a key player in the control of mammalian embryonic and somatic cell proliferation and survival. Mouse embryos lacking E4F die at an early developmental stage, whereas enforced expression of E4F1 in various cell lines inhibits cell cycle progression. E4F1-antiproliferative effects have been shown to depend on its capacity to repress transcription and to interact with pRb and p53. Here we show that full-length E4F1 protein (p120(E4F1)) but not its E1A-activated and truncated form (p50(E4F1)), interacts directly in vitro and in vivo with the LIM-only protein FHL2, the product of the p53-responsive gene FHL2/DRAL (downregulated in rhabdomyosarcoma Lim protein). This E4F1-FHL2 association occurs in the nuclear compartment and inhibits the capacity of E4F1 to block cell proliferation. Consistent with this effect, ectopic expression of FHL2 inhibits E4F1 repressive effects on transcription and correlates with a reduction of nuclear E4F1-p53 complexes. Overall, these results suggest that FHL2/DRAL is an inhibitor of E4F1 activity. Finally, we show that endogenous E4F1-FHL2 complexes form in U2OS cells upon UV-light-induced nuclear accumulation of FHL2.
Subject(s)
Homeodomain Proteins/metabolism , Muscle Proteins/metabolism , Repressor Proteins/metabolism , Transcription Factors/metabolism , Active Transport, Cell Nucleus , Adenovirus E4 Proteins/metabolism , Animals , Cell Line, Tumor , Cell Nucleus/metabolism , Cell Proliferation , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , Humans , LIM-Homeodomain Proteins , Mice , NIH 3T3 Cells , Protein Binding , Repressor Proteins/chemistry , Signal Transduction , Transcription Factors/chemistry , Transcription, Genetic , Transfection , Tumor Suppressor Protein p53/metabolism , Ubiquitin-Protein Ligases , Ultraviolet RaysABSTRACT
The aim is to study the changes of basic features of newborns' physical development in Sofia during the 20th century and to characterize the anthropometrical state of newborn infants at the beginning of the 21st century. In 2001 a total of 219 full-term clinically healthy newborns (110 boys and 109 girls) are studied. The data of stature, body weight, head and chest circumferences and thickness of three standard skinfolds (subscapular, abdomen and triceps) are analyzed. The results are compared with available literature data for Bulgarian children from representative investigations carried out during 1907, 1960, 1970, 1980 and 1990. The basic characteristics of newborns' physical development in Sofia don't change till the 60s of the past century. Between 1960 and 1970 marked body acceleration changes are present already, which abate till the 80s. After this period of the 20th century till the beginning of the 21st century, slightly deceleration changes are observed. The neonates born in Sofia during 2001 have similar values of the basic anthropometrical features to these of the neonates born at the beginning of the 20th century, and their subcutaneous fat tissue thickness is about 1/2 of this one in neonates born in 1970.