Tetratricopeptide repeat domain 9A is an interacting protein for tropomyosin Tm5NM-1

Abstract

BackgroundTetratricopeptide repeat domain 9A (TTC9A) protein is a recently identified protein which contains three tetratricopeptide repeats (TPRs) on its C-terminus. In our previous studies, we have shown that TTC9A was a hormonally-regulated gene in breast cancer cells. In this study, we found that TTC9A was over-expressed in breast cancer tissues compared with the adjacent controls (P < 0.00001), suggesting it might be involved in the breast cancer development process. The aim of the current study was to further elucidate the function of TTC9A.MethodsBreast samples from 25 patients including the malignant breast tissues and the adjacent normal tissues were processed for Southern blot analysis. Yeast-two-hybrid assay, GST pull-down assay and co-immunoprecipitation were used to identify and verify the interaction between TTC9A and other proteins.ResultsTropomyosin Tm5NM-1 was identified as one of the TTC9A partner proteins. The interaction between TTC9A and Tm5NM-1 was further confirmed by GST pull-down assay and co-immunoprecipitation in mammalian cells. TTC9A domains required for the interaction were also characterized in this study. The results suggested that the first TPR domain and the linker fragment between the first two TPR domains of TTC9A were important for the interaction with Tm5NM-1 and the second and the third TPR might play an inhibitory role.ConclusionSince the primary function of tropomyosin is to stabilize actin filament, its interaction with TTC9A may play a role in cell shape and motility. In our previous results, we have found that progesterone-induced TTC9A expression was associated with increased cell motility and cell spreading. We speculate that TTC9A acts as a chaperone protein to facilitate the function of tropomyosins in stabilizing microfilament and it may play a role in cancer cell invasion and metastasis.

Transcriptome analysis reveals genes associated with stem cell activation by physical exercise in the dentate gyrus of aged p16Ink4a knockout mice

“…A downregulated cell cycle regulator is Klhl4 , a member of the Klhl protein family, which mediates the ubiquitination of interacting proteins and activates the transcription of p21, thus resulting in the inhibition of cell cycle ( Choi et al, 2020 ); this would be consistent with the decrease of Klhl4 expression induced by running in p16 knockout dentate gyrus. Another regulator is Ttc9 , which interacts with tropomyosin, and since the primary function of tropomyosin is to stabilize actin filament, this interaction may play a role in cell shape and motility ( Cao et al, 2008 ), with a possible role in stem/progenitor cells migration ( Sun et al, 2015 ); Ttc9 downregulation may thus suggest a decreased motility of exercise-activated stem/progenitor cells in the p16 knockout dentate gyrus.…”

Ttc39c is a potential target for the treatment of lung cancer

“…The protein encoded by the Ttc39c gene contains several putative tetrapeptide repeat (TPR) domains, which form a structural motif that promotes protein-protein interactions [18]. The TPR domain affects cell cycle regulation and signal domain [19,20]. Lung cancer can activate the host immune response and trigger antibodies against tumor antigens (AAbs).…”

TTC39C may be a new target for the treatment of lung adenocarcinoma

“…The protein encoded by TTC39C gene contains several putative tetrapeptide repeat ( TPR ) domains, which is a structural motif that has been shown to contribute to protein-protein interactions [18]. TPR has been found to play a role in cell cycle regulation and signal domain [19,20]. Lung cancer can trigger host immune response and trigger antibodies against tumor antigens (AAbs).…”