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Table 1 p53-regulated target genes involved in isotretinoin’s mode of action

From: p53: key conductor of all anti-acne therapies

p53 target genes Desired and adverse drug effects
Tumor necrosis factor-related apoptosis-inducing ligand, TRAIL (TNFSF10) upregulation Sebocyte apoptosis: sebum suppression
Meibomian cell apoptosis: dry eyes
Neural crest cell apoptosis: teratogenicity
Hypothalamic cell apoptosis: depression
Intestinal cell apoptosis: inflammatory bowel disease
Insulin-like growth factor-1 receptor (IGF1R) suppression Attenuated pro-survival and mitogenic signaling of IGF-1
Androgen receptor (AR) suppression Reduced AR expression and miRNA-125b-mediated suppression of p53
IGF binding protein-3 (IGFBP3) upregulation Enhanced pro-apoptotic signalling and suppressed PPARγ signalling: attenuated lipogenesis
Cyclin-dependent kinase inhibitor 1A, p21 (CDKN1A) upregulation G1/S cell cycle arrest: Suppression of comedogenesis and sebocyte proliferation
B lymphocyte-induced maturation protein 1 (BLIMP1) (PRDM1) upregulation Increased BLIMP1-mediated c-Myc suppression reducing sebocyte differentiation
Sestrin 1 (SESN1) and sestrin 2 (SESN2) upregulation Activation of AMPK resulting in mTORC1 and ACC inhibition: sebum suppression
Forkhead box O1 (FOXO1) upregulation Suppression of AR, SREBP1c and PPARγ: suppression of lipogenesis
Forkhead box O3a (FOXO3A) upregulation Enhanced upregulation of TRAIL: enhancement of apoptosis
AMP-activated protein kinase (PRKAA1) Increased expression of AMPK and AMPK-mediated inhibition of mTORC1
Aquaporin 3 (AQP3) upregulation Increased aquaporin 3 expression: increased transepidermal water loss, dry skin, xerosis,
Aquaporin 4 (AQP4) upregulation Increased aquaporin 4 expression increasing cerebrospinal fluid (risk of pseudotumor cerebri)
Apolipoprotein B100 (APOB) and apoB mRNA editing enzyme complex 1 (APOBEC1) Increased hepatic synthesis of ApoB100: hypertriglyceridaemia with increased hepatic secretion of triglyceride-rich VLDL