Identification and characterization of a novel cell cycle-regulated internal ribosome entry site

PITSLRE protein kinases are related to the large family of cyclin-dependent kinases. They have been proposed to act as tumor suppressor genes and have been shown to play a role in cell cycle progression. We report that two PI TSLRE protein kinase isoforms, namely p110(PITSLRE) and p58(PITSLRE), are t ranslated from a single transcript by initiation at alternative in-frame AU G codons. p110(PITSLRE) is produced by classical cap-dependent translation, whereas p58(PITSLRE) results from internal initiation of translation contr olled by an internal ribosome entry site (IRES) with unique properties. The IRES element is localized to the mRNA coding region, and its activity is c ell cycle regulated, which permits translation of p58(PITSLRE) in G2/M.