TCDB is operated by the Saier Lab Bioinformatics Group

8.A.183.  The RelA-associated Inhibitor (RAI) Family 

RAI (Q9UKV5) is a regulator that plays a central role in the regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins in humans. It blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. It also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (Bergamaschi et al. 2003). Other designations include: PPP1R13L, iASPP and NKIP1. iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca2+ homeostasis and control tumor growth and drug resistance (Zheng et al. 2022). 

Ca2+ release from the endoplasmic reticulum (ER) is an essential event in the modulation of Ca2+ homeostasis, which is coordinated by multiple biological processes, ranging from cell proliferation to apoptosis. Deregulated Ca2+ homeostasis is linked with various cancer hallmarks.  Zheng et al. 2022 demonstrated that a reported Ca2+-channel protein TMCO1 (transmembrane and coiled-coil domains 1) (TC# 1.A.106.1.1) is overexpressed in colon cancer tissues at protein levels but not at messenger RNA levels. TMCO1 is a substrate of ER-associated degradation E3 ligase Gp78. Intriguingly, Gp78-mediated TMCO1 degradation at K186 is under the control of the iASPP (inhibitor of apoptosis-stimulating protein of p53) oncogene. Mechanistically, iASPP robustly reduces ER Ca2+ stores, mainly by competitively binding with Gp78 and interfering with Gp78-mediated TMCO1 degradation. A positive correlation between the iASPP and TMCO1 proteins has been validated in human colon tissues. Inhibition of iASPP-TMCO1 axis promotes cytosolic Ca2+ overload-induced apoptotic cell death and reducing tumor growth both in vitro and in vivo (Zheng et al. 2022).

This family belongs to the: Ubiquitin Ligase (UL) Superfamily .

References associated with 8.A.183 family:

Bergamaschi, D., Y. Samuels, N.J. O'Neil, G. Trigiante, T. Crook, J.K. Hsieh, D.J. O'Connor, S. Zhong, I. Campargue, M.L. Tomlinson, P.E. Kuwabara, and X. Lu. (2003). iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat. Genet. 33: 162-167. 12524540
Zheng, S., D. Zhao, G. Hou, S. Zhao, W. Zhang, X. Wang, L. Li, L. Lin, T.S. Tang, and Y. Hu. (2022). iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca homeostasis and control tumor growth and drug resistance. Proc. Natl. Acad. Sci. USA 119:. 35121659