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

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