Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration - International Review of Cell and Molecular Biology - page 234

Herp ( Liang et al., 2006 ) and EDEM ( DenBoer et al., 2005 ). Luman has
been implicated in dendritic cell maturation, a process that is regulated by
association with a complex containing the proteins DC-STAMP and OS9
( Eleveld-Trancikova et al., 2010 ). The transcriptional activity of Luman is
regulated by differential interaction with the cofactor HCF-1 (herpes sim-
plex virus-related host cell factor 1) or LRP (Luman recruitment factor),
that favor or repress transcriptional activity, respectively ( Audas et al., 2008 ).
On the other hand, OASIS/CREB3L1 is a transcription factor highly
expressed in astrocytes and osteoblasts, and like the rest of subfamily mem-
bers, is located in the ER membrane ( Kondo et al., 2005 ). OASIS displays
low homology with ATF6 in its luminal region but was described as a
target for S1P/S2P proteases in response to ER stress ( Murakami et al.,
2006 ). OASIS-deficient mice suffer from severe osteopenia and spontane-
ous fractures generated by decreased ColIaI expression ( Murakami et al.,
2009 ). CREB3L2/BBF2H7 is a transcriptional factor analogous to OASIS
that is highly expressed during the extension phase of long bones in the
chondrocytes of the proliferating zone of cartilage. In addition, CREB3L2/
BBF2H7 is expressed in other tissues, such as the lung and nervous tis-
sue ( Kondo et al., 2007 ). Sec23a, a protein required for the recruitment
of Sec13/31 and other components of the COPII vesicles, important for
vesicle trafficking from ER to Golgi, is controlled by CREB3L2 ( Saito
et al., 2009 ). CREB3L3/CREBH is expressed in hepatocytes and is also
cleaved by S1P/S2P proteases. This transcription factor is known to regu-
late the expression of the gluconeogenic enzyme PEPCK in response to
cyclic AMP and protein kinase A ( Asada et al., 2011 ). Finally, CREB3L4/
CREB4/AIbZIP/Tisp40 has been associated, among other things, with
male germ cell development and the ER stress response during spermio-
genesis ( Adham et al., 2005 ).
3.3. Integral Response or Cross Talk between Different UPR
Branches
ER stress sensors use different mechanisms and effectors to activate the
UPR, but at some points, the three pathways communicate. One example
is the close relationship between the IRE1α and ATF6 pathways. XBP1u
not only functions as a negative regulator of XBP1 but also targets the active
form of ATF6 to the proteasome ( Yoshida et al., 2009 ), while ATF6, on the
other hand, also controls the transcription of XBP1 ( Yoshida et al., 2001 ).
Additionally, ATF6 heterodimerizes with XBP1 to promote degradation of
ERAD components ( Yamamoto et al., 2007 ).