Tumor suppressing subtransferable candidate 4 (TSSC4)

Tumor suppressing subtransferable candidate 4 (TSSC4) is an imprinted, intrinsically disordered protein localized in the nucleus and associated with U5 small nuclear ribonucleoprotein (snRNP) complexes involved in pre-mRNA splicing[2][4]. TSSC4 acts as a snRNP assembly chaperone, interacting with U5-specific proteins (PRPF8, EFTUD2, SNRNP200) during both biogenesis and recycling of snRNPs, and inhibits premature events during spliceosome assembly[2][4]. TSSC4 also functions as a tumor suppressor, inhibiting cancer cell growth and tumor growth by suppressing autophagy, in part through interaction with the autophagy protein LC3 via a LC3-interacting region (LIR)[1][3]. Amplification and mutation of membrane receptor genes such as EGFR (especially EGFRvIII) upregulation TSSC4 in glioblastoma and breast cancer cells, linking EGFR signaling to autophagy regulation through TSSC4[3]. Overexpression of TSSC4 confers resistance to autophagy-inducing chemotherapy (e.g., temozolomide) in glioblastoma by preventing autophagy-induced cell death[3]. TSSC4 is encoded in a tumor suppressor imprinted domain of chromosome 11p15.5, associated with various cancers and Beckwith-Wiedemann syndrome[3][5]. Currently, no drugs specifically target TSSC4, but its expression affects response to autophagy-targeting drugs.

Other names

U5 small nuclear ribonucleoprotein TSSC4Tumor-suppressing STF cDNA 4 proteinTumor-suppressing subchromosomal transferable fragment candidate gene 4 proteinProtein TSSC4

Drugs (like temozolomide) induce autophagy-mediated cell death; TSSC4 overexpression inhibits this process, conferring drug resistance[3]; TSSC4 interacts with LC3 (autophagy protein) via its LC3-interacting region, suppressing autophagy[1][3]