TumorSuppressorproteine

Tumor suppressor proteins are a class of proteins encoded by tumor suppressor genes that help prevent cancer by restraining cell proliferation, promoting DNA repair, and triggering cell death when genomic damage is extensive. They act as guardians of the genome, maintaining cellular homeostasis and genomic integrity.

Most tumor suppressors function as part of signaling networks that sense stress, such as DNA damage or oncogene activation. Key pathways include the p53 pathway, which induces cell cycle arrest through p21 and can initiate apoptosis; the RB-p16/INK4a pathway that prevents progression from G1 to S phase; and DNA damage response networks coordinated by ATM/ATR, BRCA1/2 and related proteins that repair double-strand breaks.

Prominent examples are p53 (TP53), RB1, BRCA1, BRCA2, PTEN, and CDKN2A. These proteins can be classified as gatekeepers (directly blocking proliferation, e.g., p53, RB) or caretakers (preserving genome stability, e.g., BRCA1/2, mismatch repair genes). Inactivation of these proteins removes critical checks on growth and genome maintenance, contributing to tumor development.

Loss-of-function mutations, chromosomal deletions, or promoter silencing of tumor suppressor genes contribute to cancer. The two-hit hypothesis describes how both alleles must typically be inactivated for tumorigenesis in many sporadic cases; inherited predisposition can occur with a germline mutation. Clinical examples include Li-Fraumeni syndrome (TP53) and hereditary breast-ovarian cancer (BRCA1/2) and familial retinoblastoma (RB1). Therapeutically, strategies aim to restore tumor suppressor function or exploit vulnerabilities created by their loss, such as using PARP inhibitors in BRCA-mutant cancers.