1: J Biol Chem. 2003 Jan 10;278(2):1336-45. Epub 2002 Oct 24. 

The NF-YB/NF-YC structure gives insight into DNA binding and transcription
regulation by CCAAT factor NF-Y.

Romier C, Cocchiarella F, Mantovani R, Moras D.

Departement de Biologie et Genomique Structurales, Institut de Genetique et de
Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite Louis Pasteur, 1 Rue
Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France.

The heterotrimeric transcription factor NF-Y recognizes with high specificity
and affinity the CCAAT regulatory element that is widely represented in
promoters and enhancer regions. The CCAAT box acts in concert with neighboring
elements, and its bending by NF-Y is thought to be a major mechanism required
for transcription activation. We have solved the structure of the NF-YC/NF-YB
subcomplex of NF-Y, which shows that the core domains of both proteins interact
through histone fold motifs. This histone-like pair is closely related to the
H2A/H2B and NC2alpha/NC2beta families, with features that are both common to
this class of proteins and unique to NF-Y. The structure together with the
modeling of the nonspecific interaction of NF-YC/NF-YB with DNA and the full
NF-Y/CCAAT box complex highlight important structural features that account for
different and possibly similar biological functions of the transcriptional
regulators NF-Y and NC2. In particular, it emphasizes the role of the newly
described alphaC helix of NF-YC, which is both important for NF-Y trimerization
and a target for regulatory proteins, such as MYC and p53.

PMID: 12401788 [PubMed - indexed for MEDLINE]


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2: J Biol Chem. 2002 Oct 18;277(42):39769-76. Epub 2002 Aug 6. 

p73 independent of c-Myc represses transcription of platelet-derived growth
factor beta-receptor through interaction with NF-Y.

Hackzell A, Uramoto H, Izumi H, Kohno K, Funa K.

Department of Cell Biology, Institute of Anatomy and Cell Biology, Goteborg
University, Box 420, SE-405 30 Gothenburg, Sweden.

We recently reported that c-Myc represses the transcription of platelet-derived
growth factor (PDGF) beta-receptor (Izumi, H., Molander, C., Penn, L. Z.,
Ishisaki, A., Kohno, K., and Funa, K. (2001) J. Cell Sci. 114, 1533-1544). We
demonstrate here that the p53 family protein p73alpha represses PDGF
beta-receptor transcription essentially by the same mechanism. p73alpha but not
p73beta or p53 represses the transcription in concordance with its ability to
bind NF-YC and NF-YB. None of other p73 isoforms (i.e. p73beta, p73gamma,
p73epsilon), C-terminal deletion mutants of p73alpha, and p53 is able to bind
NF-Y with the exception of p63alpha. This finding suggests that the sterile
alpha-motif domain present only in p73alpha and p63alpha is the interaction
site. For the repression, the N-terminal transactivation domain of p73alpha is
also indispensable, arguing for the importance of the activity of p73alpha in
the mechanism. p73alpha binds the C-terminal HAP domain of NF-YC previously
found to be the interaction site with c-Myc and TBP. Because c-Myc induces and
activates p73alpha (Zaika, A., Irwin, M., Sansome, C., and Moll, U. M. (2001) J.
Biol. Chem. 276, 11310-11316) and they bind each other (Uramoto, H., Izumi, H.,
Ise, T., Tada, M., Uchiumi, T., Kuwano, M., Yasumoto, K., Funa, K., and Kohno,
K. (2002) J. Biol. Chem. 277, in press), we examined whether the repression by
p73 is dependent on c-Myc. However, Myc-null rat fibroblasts are also
susceptible to p73alpha-induced repression. Serum stimulation of NIH3T3 cells
gradually decreased the amount of endogenous NF-Y binding to the PDGF
beta-receptor promoter, whereas NF-YA expression in the nuclear extracts remains
unchanged. Our results indicate that serum stimulation induces c-Myc and
p73alpha, leading to the down-regulation of PDGF beta-receptor expression by
repressing its transcription.

PMID: 12167641 [PubMed - indexed for MEDLINE]


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