AAC-11, A NOVEL CDNA THAT INHIBITS APOPTOSIS AFTER GROWTH-FACTOR WITHDRAWAL

Many growth factors and cytokines act as cellular survival factors by preventing programmed cell death (apoptosis). However, the specific ge nes and corresponding proteins that mediate survival are poorly define d, To identify potential survival genes, a cDNA library was prepared f rom murine fibroblasts and screened by a functional expression cloning approach. A 1023-bp cDNA, AAC-11, was identified that encodes a prote in of approximately 25 kDa, The AAC-11 gene shows strong species conse rvation and is ubiquitously expressed in embryonic and adult tissues w ith multiple transcripts, as well as in various human tumor cell lines , The predicted protein contains a leucine zipper domain but lacks a D NA-binding domain, BALB/c3T3 fibroblasts that were stably transfected with AAC-11 cDNA were viable in serum-free medium for up to 12 weeks. The protective action of AAC-11 was abolished by mutation of leucines to arginines within the leucine zipper domain, We also isolated a long er AAC-11 cDNA that codes for up to an additional 290 amino-terminal a mino acids but did not protect against apoptosis, The cDNA for human A AC-11 was identified and exhibits strong homology with the murine spec ies and retains the leucine zipper domain, Western immunoblots of BALB /c3T3 cells using rabbit anti-AAC-11 polyclonal serum revealed a major native 55-kDa AAC-11 protein and a minor 25-kDa protein corresponding to the long and short forms of AAC-11 cDNA, respectively, In summary, we report a cDNA whose expression supports cell viability after withd rawal of growth factors, The corresponding native protein may function as a novel inhibitor of apoptosis.