Human endogenous retrovirus protein Rec interacts with the testicular zinc-finger protein and androgen receptor

J Gen Virol. 2010 Jun;91(Pt 6):1494-502. doi: 10.1099/vir.0.014241-0. Epub 2010 Feb 10.

Abstract

More than 2000 human endogenous retrovirus (HERV) sequences are present in the human genome, yet only a few are intact and able to produce proteins. The normal functions of these, if any, are unknown, but some HERV proteins have been implicated in cancers, in particular germ-cell cancers. For instance, it has been documented that (i) patients with germ-cell tumours frequently produce antibodies against HERV proteins; (ii) transgenic mice expressing HERV-K (HML-2) rec are prone to testicular carcinoma in situ; and (iii) Rec can bind and suppress a guardian of germline stem-cell pluripotency, the promyelocytic leukaemia zinc-finger protein (PLZF). This study identified the PLZF-related testicular zinc-finger protein (TZFP) as a binding partner of HERV-K (HML-2) Rec. Interactions occurred via the N- and C-terminal domains of Rec and the C-terminal DNA-binding zinc-finger domain of TZFP (aa 375-450). Not much is known about the function of TZFP. The protein is expressed predominantly in the testis, where it functions as a transcriptional repressor that is active during specific stages of spermatogenesis. The most intensely studied function of TZFP is that of a co-repressor of the activated androgen receptor (AR). Here, it was shown that Rec can form a trimeric complex with TZFP and AR, and can relieve the TZFP-mediated repression of AR-induced transactivation. In addition, Rec was able to overcome the direct transcriptional repression by TZFP of the c-myc gene promoter in reporter assays. Thus, HERV-K (HML-2) Rec may function as an oncoprotein by de-repressing oncogenic transcription factors such as AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Host-Pathogen Interactions*
  • Humans
  • Protein Binding
  • Protein Interaction Mapping*
  • Receptors, Androgen / metabolism*
  • Repressor Proteins / metabolism*
  • Viral Envelope Proteins / metabolism*

Substances

  • AR protein, human
  • ERVK-6 protein, human endogenous retrovirus
  • Receptors, Androgen
  • Repressor Proteins
  • TZFP protein, human
  • Viral Envelope Proteins