HUWE1-associated protein modifying stress responses 1 (HAPSTR1)

HUWE1-associated protein modifying stress responses 1 (HAPSTR1) is a highly evolutionarily conserved protein acting as a central rheostat for cellular stress response networks[1]. It is encoded by the C16orf72 gene. HAPSTR1 is inducible by multiple cellular stressors and modulates key pathways in response to genotoxic, nutrient, hypoxic, redox, and proteotoxic stress. Mechanistically, it binds to and is ubiquitinated by the E3 ligase HUWE1, which is required both for HAPSTR1’s regulatory activity and for its degradation, thus titrating the network’s response to stress[1]. HAPSTR1 is expressed as two isoforms and contains a highly conserved domain (DUF4588/HBO domain) responsible for oligomerization and HUWE1 association. Knockdown or depletion of HAPSTR1 alters global gene expression, typically up-regulating DNA damage response genes while down-regulating inflammatory and other stress response genes. HAPSTR1 is more highly expressed in tumors, particularly those with high stress burdens, indicating a role in cancer biology and resilience. Currently, there is no evidence of direct pharmaceutical targeting of HAPSTR1, but its essential function in stress coordination makes it a candidate for future therapeutic exploration in cancer and possibly other disease contexts[1][2].

Other names

HAPSTR1C16orf72Telomere attrition and p53 response 1 proteinTelomere Attrition and p53 Response 1TAPR1FLJ41272PRO0149UPF0472 protein C16orf72

Not applicable; no drugs are known that directly target HAPSTR1. It acts as a HUWE1 cofactor and is subject to HUWE1-mediated ubiquitination and degradation as part of a titration mechanism for stress response modulation