A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppresser proteins

Cyclin E-Cdk2 is an evolutionary conserved cyclin-dependent kinase (CDK) co mplex that drives the G1 to S phase transition of the cell cycle. A novel c DNA encoding a HECT family protein also containing RCC1-like repeats was is olated by a yeast two-hybrid screening using both cyclin E and its inhibito r p21. The protein product of this cDNA, Ceb1, interacts with various cycli n subunits of CDKs in mammalian cells. Expression of Ceb1 is specifically d etected in testis and ovary and is highly elevated when the functions of th e tumor suppressor proteins, p53 and RE, are compromised by mutations or vi ral oncoproteins, The present results suggest that Ceb1 may play a critical role when its expression and the CDK activity are upregulated by inactivat ion of p53 and RE. (C) 1999 Academic Press.