Document 0151
 DOCN  M9440151
 TI    Mechanism of expression and role in transcriptional control of the
       proto-oncogene NFKB-2/LYT-10.
 DT    9404
 AU    Chang CC; Zhang J; Lombardi L; Neri A; Dalla-Favera R; Department of
       Pathology, College of Physicians and Surgeons,; Columbia University, New
       York, New York 10032.
 SO    Oncogene. 1994 Mar;9(3):923-33. Unique Identifier : AIDSLINE
       MED/94151016
 AB    The NFKB-2 gene (previously LYT-10, NF-kappa Bp100 or NF-kappa Bp97)
       codes for a NF-kappa B/rel related protein which is highly homologous to
       NFKB-1 (previously NF-kappa Bp105) within its rel, poly-glycine and
       ankyrin domains. The NFKB-2 gene is a candidate proto-oncogene since it
       is involved in lymphoma-associated chromosomal aberrations. In order to
       gain insight into the physiological function and role in tumorigenesis
       of NFKB-2, we have analysed its mechanism of expression and role in
       transcriptional regulation. We report that, contrary to previous
       studies, a single 3.2 kb mRNA species and its 100 kD (p100) primary
       translation product is detectable in all cell types tested. A second
       NFKB-2 protein, p52, corresponding to the amino-terminal half (rel
       domain) of NFKB-2 p100, is detectable in the same cell types and derives
       from the post-translational processing of p100. While p100 is
       constitutively localized in the cytoplasm, NF-kappa B induction by TPA
       treatment of Hela cells is associated with cytoplasmic/nuclear
       translocation of NFKB-2 p52 and its appearance within DNA-binding
       NF-kappa B complexes. NFKB-2 p52 differs from NFKB-1p50 in its
       differential affinity for kappa B sequences: by itself it binds
       H2/HLA-kappa B sites more efficiently than HIV/IgK-kappa B sites, while
       it can bind both sites efficiently when complexed with Rel-A(p65).
       Transient co-transfection of expression and reporter plasmids in cells
       devoid of endogenous NF-kappa B activity showed that p52 has no
       intrinsic transcriptional activation capabilities: it can stimulate
       Rel-A(p65)-driven transcription by formation of p65/p52 heterodimers,
       whereas, overexpressed, it down-regulates p65-dependent transcription by
       formation of inactive p52/p52 homodimers. These results indicate that
       the NFKB-2 gene codes for an inducible NF-kappa B transcription factor
       with the capability of differentially regulating NF-kappa B
       transcription depending on its abundance in the nucleus.
 DE    Amino Acid Sequence  Base Sequence  Cell Nucleus/DRUG EFFECTS/METABOLISM
       DNA/METABOLISM  *Gene Expression Regulation  Hela Cells  Human
       Molecular Sequence Data  NF-kappa B/*GENETICS/PHYSIOLOGY  Protein
       Binding  Protein Processing, Post-Translational  *Proto-Oncogenes  RNA,
       Messenger/GENETICS  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  *Transcription, Genetic
       Translation, Genetic  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).