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. 2019 Oct 15;6(6):e1677140.
doi: 10.1080/23723556.2019.1677140. eCollection 2019.

p16: cycling off the beaten path

Raquel Buj  1 , Katherine M Aird  1
Affiliations

p16: cycling off the beaten path

Raquel Buj et al. Mol Cell Oncol. .

Abstract

p16INK4A (hereafter called p16) is a faithful cellular ally in the fight against tumorigenesis. Although its canonical pathway through retinoblastoma (RB) is well delineated, RB-independent functions for p16 are beginning to emerge. Here we summarize non-canonical roles of p16, including our recent finding on its role in nucleotide metabolism.

Keywords: AP-1; JNK1/3; NF-κB; Retinoblastoma; SP1; cell cycle; mTORC1; nucleotide metabolism; reactive oxygen species; senescence.

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Figures

Figure 1.
Figure 1.
Canonical and non-canonical p16 signaling. Schematic showing the p16 canonical (red) and non-canonical (black) pathways, including: p16–Retinoblastoma (RB) pathway; p16 regulation of nucleotide metabolism through the mammalian target of rapamycin complex 1 (mTORC1); p16 directly binds to p65 and inhibits the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) complex; p16 regulation of intracellular oxidative stress; p16 regulation of mitochondrial biogenesis (PRC: PGC-1-related coactivator; TFAM: Transcription Factor A, Mitochondrial); p16 directly binds to mitogen-activated protein kinases (JNK1/3) and regulates the activating protein-1 (AP1) transcription factor activity; p16 directly binds the eukaryotic translation elongation factor 1 alpha 2 (eEF1A2) and inhibits protein translation; and p16 forms a complex with the cyclin-dependent kinase 4 (CDK4) and SP1 transcription factor that promotes the transcription of tumor-suppressive miRNAs.
See this image and copyright information in PMC

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