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OCT4 is a key transcription factor in maintaining the pluripotency and self‐renewal of embryonic stem cells (ESCs). Human  OCT4  gene can generate three mRNA isoforms (OCT4A, OCT4B, and OCT4B1) by alternative splicing and four protein isoforms (OCT4A, OCT4B‐265, OCT4B‐190, and OCT4B‐164) by alternative splicing or alternative translation initiation. OCT4A is a transcription factor responsible for the stemness of ESCs, while the function of OCT4B protein isoforms is still not clear. We have previously reported that OCT4B‐190 functioned in cell stress response. Here, we present another product of  OCT4  gene, OCT4B‐265, which is upregulated under genotoxic stress in stem cells, and it may function in stress response through p53 signaling pathway. This work gives an insight into the novel function of OCT4B protein isoforms and helps us to understand the complex expression patterns and biological functions of  OCT4  gene. S TEM  C ELLS   2012; 30:665–672

The Novel Function of OCT4B Isoform‐265 in Genotoxic Stress