C terminus controls enzymatic activity and immortalization. (A) C terminus of hTERT dictates activity level. TRAP analysis of BJT cells that were transduced with retroviruses expressing HHM, MMH, hTERT, and mTERT (IC, internal control). (B) Serial passage of cells in panel A shows that the C terminus of hTERT is necessary and sufficient for immortalization. (C and D) Telomeres shorten in HHM-BJT cells, leading to crisis. Telomeres shorten and then stabilize in immortally proliferating MMH-BJT cells for up to 150 population doublings by TRF Southern blot analysis.