The MYB-related transcription factor MYPOP acts as a selective regulator of cancer cell growth.

The MYB-related transcription factor and partner of profilin (MYPOP or p42POP) is a ubiquitously expressed yet understudied protein recently identified as a restriction factor of oncogenic human papillomaviruses (HPV) and proposed tumor suppressor. Here we show that in HPV-transformed cervical cancer cells, MYPOP induces alterations in cell morphology, silences viral and cellular oncogenes including E6 and MYC, and stimulates the release of the cancer-killing cytokine interleukin-24. Transcriptomic and live-cell analyses reveal a rapid G1/S-phase arrest followed by loss of viable cervical cancer cells and induction of apoptosis. Moreover, MYPOP expression is broadly diminished across multiple human cancers, and its re-expression by both DNA- and mRNA-gene transfer markedly suppresses tumor cell proliferation while sparing normal epidermal keratinocytes. Similarly, murine Mypop inhibits mouse cancer cell growth. Collectively, our findings identify MYPOP as a selective suppressor of tumor cell proliferation across species in vitro and point to its potential relevance for future therapeutic investigation.