TEX26 (Testis Expressed 26)

Recent evidence shows that ER-phagy receptors can form novel ER-derived structures, such as ER-tubular bodies (ER-TBs) consisted of ATL3 and RTN3L, which mediate Golgi-bypassing unconventional protein secretion under stress conditions, revealing non-degradative functions of these receptors beyond quality control. Targeting ER-phagy receptors may provide insights into potential therapeutic strategies for diseases associated with this fundamental cellular process.

Furthermore, the high-dose Cor significantly downregulated the expression levels of phosphorylated(p)-eIF2α/eIF2α, activating transcription factor 4(ATF4), glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), nuclear factor-κB(NF-κB), Bcl-2-associated X protein(Bax), and testis expressed gene 264(Tex264), while upregulating the expression level of B-cell lymphoma-2(Bcl-2). In conclusion, Cor inhibits the formation of macrophage-derived foam cells by regulating the expression of proteins in the eIF2α-ATF4-Tex264 signaling pathway, thereby suppressing ERS-induced excessive ER-phagy and apoptosis in macrophages.

High levels of NFXL1 are negatively correlated with MHC-I protein expression and predicts poor patient prognosis. These data highlight an ER resident capture complex tasked with sequestration and degradation of non-conformational MHC-I in PDAC cells, and targeting this complex has the potential to increase PDAC immunogenicity.

While DNA is traditionally repaired in the nucleus, Lascaux et al. reveal a novel role for the lysosome in DNA repair, demonstrating that topoisomerase 1 (TOP1) cleavage complex (TOP1cc) DNA lesions are degraded via TEX264-mediated selective autophagy.

Mechanistically, the autophagy receptor TEX264 acts as a TOP1cc sensor at DNA replication forks, triggering TOP1cc processing by the p97 ATPase and mediating the delivery of TOP1cc to lysosomes in an MRE11-nuclease- and ATR-kinase-dependent manner. We found an evolutionarily conserved role for selective autophagy in DNA repair that enables cell survival, protects genome stability, and is clinically relevant for colorectal cancer patients.

Few of the candidate genes observed in HSP (ITPA, MBP, PPP4R12, and SPOCK3) have been previously implicated in leukemia. The findings suggest that the methylation signatures and mutation spectrum for HSP and NHW pediatric acute ALL patients might differ and further studies among HSP, a group with the highest prevalence of acute pediatric ALL, could potentially identify new genetic and epigenetic markers for acute pediatric ALL.