Rhabdoid Tumor : Role of SMARCB1 (INI1)

Comments:
Role of SMARCB1: SMARCB1 protein plays a critical role in epigenetic regulation, cell cycle progression and crosstalk between signaling cascades as discussed in this and next several images.

SMARCB1 acts by signaling through the p16INK4a and RB tumor suppressor genes to prevent cell cycle progression from G0/G1 to the S-phase.

SMARCB1 represses Cyclin D1 transcription and inhibits the action of cyclin-dependent kinases (CDK4/6) by directly binding and recruiting histone deacetylase (HDAC) activity in G1 of the cell cycle. This causes hypophosphorylation of RB and induction of p16(INK4A), another tumor suppressor gene.

Loss of SMARCB1 function causes uncontrolled cell proliferation. Reintroduction of SMARCB1/INI1 into malignant rhabdoid tumor cell lines with SMARCB1/INI1 deficiency induces accumulation of cells in G0/G1, and, in some cases, causes cell senescence or apoptosis.

Image source: Kalimuthu SN, Chetty R. Gene of the month: SMARCB1. J Clin Pathol 2016; 69:484-489; used under Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license.