Transducer of erbB-2 1 (TOB1)

Transducer of erbB-2 1 (TOB1) is a member of the BTG/TOB family of anti-proliferative proteins that function as transcriptional corepressors and tumor suppressors. TOB1 regulates cell cycle progression, mainly by inhibiting transition from G1 to S phase, modulating key signaling pathways such as MAPK/ERK and interacting with cell cycle regulators and transcription factors. It inhibits cell proliferation, particularly in immune cells and cancer cells, and is frequently downregulated or functionally inactivated in various cancers, where its loss is associated with increased tumor growth and radioresistance. TOB1 can shuttle between the nucleus and cytoplasm, with its localization influencing its function; it is subject to regulation by MAPK-mediated phosphorylation which attenuates its anti-proliferative activity. Mechanistically, TOB1 overexpression sensitizes tumor cells to radiotherapy by enhancing DNA damage response and impairing DNA repair, primarily via modulation of MAPK/ERK signaling independent of EGFR inhibition. Its expression or function can serve as a biomarker for cancer prognosis and radiosensitivity. No drugs directly target TOB1 clinically, but it is an area of experimental therapeutic interest, particularly for enhancing cancer treatment efficacy and overcoming resistance to EGFR inhibitors.

Other names

Protein Tob1TOBTROB1TROBAPRO5APRO6PIG49Proliferation-inducing gene 49Transducer of erbB2 1

Drugs or interventions that increase TOB1 expression or activity enhance anti-proliferative signaling, potentially sensitizing cancer cells to radiotherapy or inhibiting growth. Downregulation or loss of TOB1 contributes to increased cell proliferation and cancer risk. Targeting the MAPK/ERK pathway can modulate TOB1 phosphorylation, affecting its tumor suppressor activity.