Biology Reference
In-Depth Information
Ala394Thr polymorphism in NPAS2 has been proposed as a biomarker for
non-Hodgkin's lymphoma (
Zhu et al., 2007
). Some proofs of a correlation
between NPAS2 and breast cancer have been reported (
Yi et al., 2010; Zhu
et al., 2008
). Indeed, NPAS2 might have a putative tumour suppressor func-
tion (
Hoffman, Zheng, Ba, & Zhu, 2008
), and its cancer-related transcrip-
tional targets have been identified (
Yi, Zheng, Leaderer, Hoffman, & Zhu,
2009
). Other research groups, on the contrary, support the hypothesis that it
is not possible to incontrovertibly prove any significant direct association
between NPAS2 aberrant function and breast cancer risk, as data are still
ambiguous (
Wang et al., 2011
).
2.2.1.3 The mammalian Period protein 2
Recently, another haem-binding protein, homologous to NPAS2 (18%
identity and 58% similarity between the PAS domains), has been identified
in mouse, namely, mammalian Period protein 2 (mPER2) (
Kaasik & Lee,
2004
). mPer1 and mPer2 are mammalian Period genes involved in the cir-
cadian clock whose expression is controlled by haem. mPER2 and NPAS2
function in concert and their activities are strictly interdependent. It has been
shown that when the haem group is synthesized, there is competition
between mPER2 and NPAS2 for its binding. It has been proposed that a
haem-exchange between them is a critical step to regulate the genes target
transcription (
Kaasik & Lee, 2004
).
mPER2 contains two PAS domains, PAS-A and PAS-B (
Hayasaka,
Kitanishi, Igarashi, & Shimizu, 2011; Kitanishi et al., 2008
). In particular,
PAS-B mediates the protein-protein interactions between transcription fac-
tors (
Hayasaka et al., 2011
).
2.2.1.4 The CO-responsive transcription regulator of Burkholderia
xenovorans (BxRcoM)
Haem-binding transcription factors have been identified also in Bacteria. In
the bacterium
B. xenovorans
, two proteins have been isolated,
Bx
RcoM-1
and
Bx
RcoM-2, which function as CO-dependent transcription factors
in vivo
and stimulate the expression of genes for aerobic CO metabolism.
Both these proteins show an N-terminal haem-binding PAS domain and
a C-terminal LytTR DNA-binding domain (
Kerby, Youn, & Roberts,
2008
). A unique feature for these proteins is the coordination with a cysteine
residue (Cys94) as distal axial ligand (
Marvin, Kerby, Youn, Roberts, &
Burstyn, 2008; Smith et al., 2012
). Nothing can be commented about the
architecture of these proteins as structural data have yet to be reported.
