Intracellular localization of the tumor suppressor HtrA1/Prss11 and its association with HPV16 E6 and E7 proteins

We have a long-standing interest in a nuclear protease which appears to be involved in carcinogenesis. We recently identified the protease as high temperature requirement factor A 1 (HtrA1), also known as Prss11, which is member of an oxidative stress-response family of proteases. HtrA1 has been classified as a secreted protease involved in TGFβ signaling, but recent work has shown HtrA1 to be a tumor suppressor. Here we show that processed forms of HtrA1 are found intracellularly and intranuclearly, and the active intranuclear form of HtrA1 shows an ∼Mr 29,000. Further, expression of HPV E6/E7 proteins is associated with a post-transcriptional up-regulation of HtrA1 (most notably the nuclear form), and HtrA1 is found associated with both HPV E6 and E7 proteins.