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OCT4 is a pivotal transcription factor in maintaining the pluripotency and self‐renewal capacities of embryonic stem (ES) cells. Human  OCT4  can generate two isoforms by alternative splicing, termed OCT4A and OCT4B. OCT4A confers the stemness properties of ES cells, whereas the function of OCT4B is unknown. We present here the diverse protein products and a novel function of  OCT4  gene. A single OCT4B mRNA can encode three isoforms by alternative translation initiation at AUG and CUG start codons, respectively. A putative internal ribosome entry site (IRES) has been identified in OCT4B mRNA accounting for the translation mechanism. The OCT4B‐190 is upregulated under stress conditions and it may protect cell against apoptosis under stress. This work evokes the significance to distinguish the biological function of the protein products of  OCT4 . The  OCT4  gene, by the regulation of alternative splicing and alternative translation initiation, may carry out more crucial roles in many biological events. S TEM  C ELLS  2009;27:1265–1275

Alternative Translation of OCT4 by an Internal Ribosome Entry Site and its Novel Function in Stress Response