TOR signaling pathway regulator (TIPRL)

TOR signaling pathway regulator (TIPRL) is an evolutionarily conserved regulatory protein that inhibits the catalytic activity of the PP2A family of serine/threonine phosphatases, including PP2A, PP4, and PP6[1][4][5][6]. Unlike its yeast ortholog (Tip41), which mainly sequesters proteins to inhibit TOR signaling, human TIPRL positively regulates mTORC1 activity following amino acid stimulation[1][3]. TIPRL is critical for controlling DNA damage response (ATM/ATR signaling), apoptosis, and cell proliferation, largely by influencing PP2A activity[2][3][7]. Dysregulation of TIPRL—either overexpression or knockdown—has been observed in various cancers, including hepatocellular carcinoma, where it may promote tumor cell survival or, paradoxically, sensitize cells to apoptosis depending on the context[2][3][7]. The structure of TIPRL reveals a novel protein fold capable of binding to the PP2A C-terminal tail and inhibiting PP2A holoenzyme assembly and function[1][3]. Its exact pathological and therapeutic roles remain actively investigated, especially concerning cancer and cell signaling regulation.

Other names

TIP41-like proteinTIPMGC3794dJ69E11.3TIP41TIPRL1Putative MAPK-activating protein PM10Type 2A-interacting protein

Inhibition of catalytic activity of PP2A, PP4, and PP6, affecting downstream signaling pathways (mTOR, ATM/ATR, AMPK)