The　intermediate　filament　protein　keratin　17　(Krt17)　shows　highly　dynamic　and　inducible　expression　in　skin　physiology　and　pathology.　Because　Krt17　exerts　physiologically　important　functions　beyond　providing　structural　stability　to　keratinocytes　whereas　abnormal　Krt17　expression　is　a　key　feature　of　dermatoses　such　as　psoriasis　and　pachyonychia　congenita,　the　currently　unclear　regulation　of　Krt17　expression　needs　to　be　better　understood.　Using　a　rat　model　of　radiation　dermatitis,　we　report　here　that　Krt17　expression　initially　is　down-regulated　but　later　is　strongly　up-regulated　by　ionizing　radiation.　The　early　down-regulation　correlates　with　the　activation　of　p53　signaling.　Deletion　of　p53　abolishes　the　initial　down-regulation　but　not　its　subsequent　up-regulation,　suggesting　that　p53　represses　Krt17　transcription.　Because　previous　work　reported　up-regulation　of　Krt17　by　ultraviolet　irradiation,　which　also　activates　p53　signaling,　the　effect　of　ultraviolet　radiation　was　reexamined.　This　revealed　that　the　initial　down-regulation　of　Krt17　is　conserved,　but　the　up-regulation　comes　much　faster.　Chromatin　immunoprecipitation　analysis　in　vivo　and　electromobility　shift　assay　in　vitro　identified　two　p53-binding　sites　in　the　promoter　region　of　Krt17.　Thus,　p53　operates　as　a　direct　Krt17　repressor,　which　invites　therapeutic　targeting　in　dermatoses　characterized　by　excessive　Krt17　expression.