Human endogenous retrovirus protein Rec interacts with the testicular zinc-finger protein and androgen receptor.
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.
Institute of Virology, Building 47, University of Saarland Medical School, 66421 Homburg/Saar, Germany.
Sabine
S
Kaufmann
Marlies
M
Sauter
Martina
M
Schmitt
Bianca
B
Baumert
Barbara
B
Best
Annette
A
Boese
Klaus
K
Roemer
Nikolaus
N
Mueller-Lantzsch
D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011944:Receptors, Androgen / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*
C410798:AR protein, human; C485839:ERVK-6 protein, human endogenous retrovirus; D011944:Receptors, Androgen; D012097:Repressor Proteins; D014759:Viral Envelope Proteins; C498646:ZBTB32 protein, human