Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jan;9(1):134-43.

Role of p58IPK in Endoplasmic Reticulum Stress-associated Apoptosis and Inflammation

Evgenii Boriushkin  1 , Josh J Wang  1 , Sarah X Zhang  2
Affiliations

Role of p58IPK in Endoplasmic Reticulum Stress-associated Apoptosis and Inflammation

Evgenii Boriushkin et al. J Ophthalmic Vis Res. 2014 Jan.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Activation of the URP and p58IPK. There are three branches of the UPR through which eukaryotic cells react to ER stress. In response to an increased level of unfolded proteins in the ER, PERK and IRE1 are activated by oligomerization and autophosphorylation. Activated PERK phosphorylates eIF2α leading to global protein attenuation. Lower global protein synthesis reduces ER unfolded protein load but increases production of ATF4 and CHOP. Activated IRE1 removes introns from the XBP1mRNA resulting in activation of XBP1 and induction of ER chaperones such as p58IPK. Upon ER stress, ATF6 translocates to the Golgi complex, where it undergoes two-step cleavage by site-1 and site-2 proteases. Cleaved ATF6 then translocates to the nucleus and activates a subset of UPR genes encoded chaperones, XBP1 and CHOP.
Figure 2
Figure 2
The interaction between p58IPK and GRP78. p58IPK TRP domains associate with unfolded proteins in the ER lumen. The complex then binds GRP78 via the DNAJ domain and ATPase domain. This interaction is ATP-dependent; P58IPK associates with GRP78 only in the presence of ATP and their dissociation is dependent on the hydrolyzation of ATP to ADP, resulting in a conformal change of GRP78.
Figure 3
Figure 3
P58IPK and ER stress-mediated apoptosis. During ER stress, activated PERK phosphorylates eIF2α resulting in an increased production of ATF4 and upregulation of CHOP. Active IRE1 forms a complex with adaptor molecule TRAF2. The complex recruits apoptosis-signal-regulating kinase (ASK1), which phosphorylates and activates JNK. Both CHOP and JNK function as pro-apoptotic molecules. Caspase-12, which is localized on the cytoplasmic side of the ER in resting cells, is also activated by ER stress and implicated in promoting apoptosis. P58IPK suppresses CHOP activation likely through inhibition of PERK activation, while its effect on other ER stress-related apoptotic pathways remains unclear.
Figure 4
Figure 4
p58IPK and UPR-associated inflammatory signaling pathways. During ER stress, activated IRE1 forms a complex with TRAF2 and activates IKK. Activated IKK leads to IκB degradation and subsequent activation of NF-κB, which transcribes pro-inflammatory genes. Furthermore, the IRE1-TRAF2 complex activates JNK and consequently activates other pro-inflammatory transcription factors. Activated PERK promotes NF-κB activation via translational attenuation of IκB. p58IPK attenuates the PERK/CHOP pathway through inhibition of PERK activity.
See this image and copyright information in PMC

References

    1. Yoshida H. ER stress and diseases. FEBS J. 2007;274:630–658. - PubMed
    1. Wu J, Kaufman RJ. From acute ER stress to physiological roles of the unfolded protein response. Cell Death Differ. 2006;13:374. - PubMed
    1. DuRose JB, Tam AB, Niwa M. Intrinsic capacities of molecular sensors of the unfolded protein response to sense alternate forms of endoplasmic reticulum stress. Mol Biol Cell. 2006;17:3095–3107. - PMC - PubMed
    1. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, et al. IRE1 signaling affects cell fate during the unfolded protein response. Science. 2007;318:944–949. - PMC - PubMed
    1. Calnexin, calreticulin and the folding of glycoproteins. Trends Cell Biol. 1997;7:193–200. - PubMed

LinkOut - more resources