Page 140 - D. Cancer biology

[D. Cancer biology-90]

The role and interaction of HPV E7 and PTPN14 in cervical

cancer

Min Wook Kim¹˙#, Hye Yeoung Yun²˙#, Won Kon Kim¹, Sang Chul Lee¹, Kwang Hee Bae¹, Bonsu Ku²˙*,
Seung Jun Kim²˙*, Eun-Woo Lee¹˙*

¹Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon

34141, Korea, Republic of, ²Disease Target Structure Research Center, Korea Research Institute of Bioscience and
Biotechnology (KRIBB), Daejeon 34141, Korea, Republic of

Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation,

including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded
oncoproteins, and directs recruitment and subsequent degradation of tumor-suppressive proteins such as pRb, via

its LxCxE motif. Herein, we present the crystal structure of the E7 C-terminal domain of HPV18 belonging to the
high-risk HPV genotypes bound to the catalytic domain of human PTPN14. Disruption of HPV18 E7 binding to

PTPN14 by structure-based mutagenesis impaired E7’s ability to promote keratinocyte proliferation and migration.
Likewise, E7 binding-defective PTPN14 was resistant for degradation via proteasome, and it was much more effective

than wild type PTPN 14 in attenuating Hippo signaling and negatively regulating cell proliferation, migration, and
invasion, when examined in HPV18-positive HeLa cells. These results therefore demonstrated the significance and

therapeutic potential of the intermolecular interaction between HPV E7 and host PTPN14 in HPV-mediated cell
transformation and tumorigenesis.