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Crosstalk between Mutant p53 and p62/SQSTM1 Augments Cancer Cell Migration by Promoting the Degradation of Cell Adhesion Proteins

ABSTRACT: In the present study, we set out to explore mechanisms of mutp53 GOF by identifying new interaction partners of mutp53. Specifically, we focused on the DNA contact mutant p53R273H, one of the most common p53 hotspot mutants and the most frequent TP53 mutant in pancreatic cancer. We now report that p53R273H binds selectively to the polyubiquitin-binding protein SQSTM1/p62. The crosstalk between p53R273H and p62 leads to proteasomal degradation of several cell adhesion-associated proteins, apparently in conjunction with the Golgi apparatus, resulting in loss of cell-cell junctions and enhancement of cancer cell scattered migration and invasion. This new mechanism, which does not rely on transcriptional regulation by mutp53, is likely to contribute to mutp53 GOF in tumors whose spead is reliant on scattered cell migration.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Tamar Ziv

LAB HEAD: Moshe Oren

PROVIDER: PXD029518 | Pride | 2022-03-31

REPOSITORIES: Pride

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			Action	DRS
	66683txt.rar	Other
	Seq66685_HFX.raw	Raw
	Seq66686_HFX.raw	Raw
	Seq66687_HFX.raw	Raw
	Seq66688_HFX.raw	Raw

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