TCAB1: a key promoter of tumor growth through telomere maintenance and senescence evasion.

Abstract

TCAB1 (telomerase Cajal body protein 1), encoded by the WRAP53 gene on chromosome 17p13.1, is a molecular scaffold critical for protein-nucleic acid interactions. In normal cells, TCAB1 plays a pivotal role in localizing telomerase to Cajal bodies, thereby ensuring proper telomere maintenance and genomic stability. In cancer cells, however, TCAB1 is frequently overexpressed, which supports unchecked proliferation and therapy resistance. Conversely, knockdown of TCAB1 triggers multiple tumor-suppressive mechanisms, including G1 cell cycle arrest - mediated by impaired p21 ubiquitination and subsequent Cyclin E/CDK2 inactivation - as well as telomere shortening and genomic instability due to mitochondrial dysfunction and defective DNA repair. Notably, the induction of cellular senescence emerges as a key anticancer mechanism upon TCAB1 depletion, particularly in early-stage tumors retaining wild-type p53. This review delineates the dual roles of TCAB1, highlighting its function as a context-dependent oncoprotein and the therapeutic potential of targeting it to induce senescence.