Annual Report 2011 - Center for Advanced Biotechnology and ...

(CHINJ, CINJ and CABM) and Lauri Goodell (RWJUH) characterized the effects
of mesenchymal stromal cell (MSC) on the survival and drug resistance of
primary mantle cell lymphoma (MCL) cells, an aggressive subtype of non-
Hodgkin’s lymphoma. Studies revealed an important role for the canonical and
non-canonical NF-kB pathways and expression of cytokine BAFF by MSC in the
long term survival of MSC. A manuscript was submitted (Medina et al.
Submitted).
Finally, we pursued our collaborative work with Dr. Eileen White (CINJ) on the
role of autophagy in tumorigenesis and the role of NF-kB in this context. These
studies uncovered that activated Ras, commonly found in human tumors, requires
autophagy to maintain oxidative metabolism and tumorigenesis. This suggests
that therapeutic strategies to inhibit autophagy could perhaps be useful for the
treatment of cancers in which Ras is activated. This work was published (Guo et al.
2011). Ongoing studies focus on understanding how p62 modulates autophagy and
tumorigenesis and the role of NF-kB in this context, expressed and purified active
fragment was crystallized and the structure determined by X-ray crystallography.
Seven related conformational states were obtained in the crystal. Position
differences of the oligonucleotide/oligosaccharide (OB) binding fold lid domain
over the conserved GTP binding site in the seven structures provided snapshots of
the opening and closing of the active site cleft via a swivel motion. While the
GTP binding site is structurally and evolutionarily conserved, the overall GTase
mechanism in mammalian and yeast systems differs somewhat. Experiments are
underway to crystallize complexes of human GTase with CTD and RNA as well
as GTP. Protein engineering is being applied in an effort to crystallize the full
length human CE.
CAPER co-localizes
with splicing factor
SC35 in breast
cancer cells, as seen
by
immunofluorescence
and confocal
microscopy.
13