TRIM28 osuus syövässä pohdinnassa

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574234/

Netistä löytyy useita kuvaehdotelmia  KRAB-ZFP-KAP-1 repression pathway -aiheesta.
(KAP-1 onTRIM28)
KRAB-domeeni rekrytoi TRIM28, joka tuo mukanaan  tärkeitä interaktiodomaaneja.   kuten HP1 box, PHD-domeenin ja BROMO-domeenin  (RBCC:n lisäksi) . KRAB tekee interaktion RBBCC domeeniin .  KAP-1 ( KRAB-ssssosioitunut) proteiini sitoutuu intrageeniseen kohtaan monta kb  promoottorista.
HP1-box jaksossa on PXVXL motiivi joka tekee interaktion HP1 heterokromatiiniproteiiniin1.

TRIM28 löydettiin 1966 ja sitä on tutkittu intensiivisesti ja koetettu selvittää onko se tuumorisuppressiivinen vai tuumorin kasvua edistävä. On viitettä siihen että se säätyy tuumoreissa ylös ja on huonon prognoosin emrkki.


Esim.  https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcTP-kpn21fWcjGhTQF63IzuXdfg0LAoJSxVbnL7aSiioP_BV_shQQ
 



Since the first discovery in 1996, the engagement of TRIM28 in distinct aspects of cellular biology has been extensively studied resulting in identification of a complex nature of TRIM28 protein. In this review, we summarize core biological functions of TRIM28 that emerge from TRIM28 multi-domain structure and possessed enzymatic activities.

Moreover, we will discuss whether the complexity of TRIM28 engagement in cancer biology makes TRIM28 a possible candidate for targeted anti-cancer therapy. Briefly, we will demonstrate the role of TRIM28 in regulation of target gene transcription, response to DNA damage, downregulation of p53 activity, stimulation of epithelial-to-mesenchymal transition, stemness sustainability, induction of autophagy and regulation of retrotransposition, to provide the answer whether TRIM28 functions as a stimulator or inhibitor of tumorigenesis.

 To date, number of studies demonstrate significant upregulation of TRIM28 expression in cancer tissues which correlates with worse overall patient survival, suggesting that TRIM28 supports cancer progression. Here, we present distinct aspects of TRIM28 involvement in regulation of cancer cell homeostasis which collectively imply pro-tumorigenic character of TRIM28. Thorough analyses are further needed to verify whether TRIM28 possess the potential to become a new anti-cancer target.