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Kletki linii HaCaT yavlyayutsya rasprostranennoy model'yu dlya issledovaniya normal'nykh keratinotsitov cheloveka. Odnako dlya kletok etoy linii kharakterny mutatsii v gene TP53, chto sushchestvenno skazyvayetsya na funktsiyakh kodiruyemogo belka. Osobennosti dannogo regulyatornogo kontura neobkhodimo uchityvat' pri ispol'zovanii kletok HaSaT v kachestve ob"yekta issledovaniy fiziologii i patologii kozhi cheloveka in vitro. Tsel'yu issledovaniya bylo izuchit' osobennosti realizatsii programmy differentsirovki v kletkakh linii HaCaT v usloviyakh modulyatsii aktivnosti belka r53. Snizheniya urovnya ekspressii r53 dobivalis' nokdaunom gena TR53 s pomoshch'yu shRNA (v 2,2 raza, p &lt; 0,05), i, naprotiv, uvelicheniya kontsentratsii aktivnykh form dannogo belka v kletkakh dostigali za schet vozdeystviya na kletki Nutlin-3a — ingibitora MDM2, osnovnogo negativnogo regulyatora r53. Ustanovleno, chto regulyatsiya kak minimum trekh markerov differentsirovki, SASP14, IVL (uvelicheniye ekspressii v 3,9 i 3,7 raza sootvetstvenno pri nokdaune p53, p &lt; 0,05) i TGM1 (umen'sheniye ekspressii vdvoye pri nokdaune TR53 i uvelicheniye v 1,7 raza pri vozdeystvii na kletki Nutlin-3a, p &lt; 0,05), v kletkakh HaCaT zavisit ot aktivnosti p53. Pri etom v otnoshenii ekspressii TGM1 i p53 otmechena pryamaya zavisimost', kotoraya, vozmozhno, realizuyetsya oposredovanno, cherez izmeneniye ekspressii DNp63. V to zhe vremya modulyatsiya aktivnosti p53 ne privodit k znachitel'nym izmeneniyam ekspressii tsitokeratinov.

Vliyaniye modulyatsii aktivnosti r53 na vzaimodeystviye chlenov semeystva r53 v protsesse differentsirovki keratinotsitov linii NaSaT