%0 Journal Article
%T Coordinate regulation of RARgamma2, TBP, and TAFII135 by targeted proteolysis during retinoic acid-induced differentiation of F9 embryonal carcinoma cells
%A Lucia Perletti
%A Eliezer Kopf
%A Lucie Carr¨¦
%A Irwin Davidson
%J BMC Molecular Biology
%D 2001
%I BioMed Central
%R 10.1186/1471-2199-2-4
%X We show that the RNA polymerase II transcription factor TFIID subunits TBP and TAFII135 are selectively depleted in extracts from differentiated F9 cells. In contrast, TBP and TAFII135 are readily detected in extracts from differentiated F9 cells treated with proteasome inhibitors showing that their disappearance is due to targeted proteolysis. This regulatory pathway is not limited to F9 cells as it is also seen when C2C12 myoblasts differentiate into myotubes. Targeting of TBP and TAFII135 for proteolysis in F9 cells takes place coordinately with that previously reported for the RAR¦Ã2 receptor and is delayed or does not take place in RAR mutant F9 cells where differentiation is known to be impaired or abolished. Moreover, ectopic expression of TAFII135 delays proteolysis of the RAR¦Ã2 receptor and impairs primitive endoderm differentiation at an early stage as evidenced by cell morphology, induction of marker genes and apoptotic response. In addition, enhanced TAFII135 expression induces a novel differentiation pathway characterised by the appearance of cells with an atypical elongated morphology which are cAMP resistant.These observations indicate that appropriately timed proteolysis of TBP and TAFII135 is required for normal F9 cell differentiation. Hence, in addition to transactivators, targeted proteolysis of basal transcription factors also plays an important role in gene regulation in response to physiological stimuli.RNA polymerase II (pol II) transcription factor TFIID comprises the TATA-binding protein (TBP) and a set of TBP-associated factors (TAFIIs) [[1-3]]. At least 12 TAFIIs have been identified in TFIID and cloning of their cDNAs has shown an evolutionary conservation of TAFIIs from yeast to mammals [[4-7]]. TAFIIs are not only components of the TFIID complex, but a subset of TAFIIs are also found in the SAGA, PCAF, TFTC/STAGA complexes which lack TBP [[8-12]].TAFII function in living cells has been studied in yeast where the use of temperature sensi
%U http://www.biomedcentral.com/1471-2199/2/4