AI Article Synopsis
- Endosomal sorting complexes required for transport (ESCRTs) are vital for breaking down certain receptors linked to cell growth, a process that can fail in cancer.* -
- The tumor suppressor phosphatase HD-PTP is key in managing the sorting of these receptors through its interaction with ESCRT-I subunit UBAP1.* -
- Recent studies using X-ray crystallography reveal that the coiled-coil domain of HD-PTP is rigid and open, differing from a similar regulator, Alix, and highlight how HD-PTP and UBAP1 work together, offering new insights for potential cancer therapies.*
Article Abstract
Endosomal sorting complexes required for transport (ESCRTs) are essential for ubiquitin-dependent degradation of mitogenic receptors, a process often compromised in cancer pathologies. Sorting of ubiquinated receptors via ESCRTs is controlled by the tumor suppressor phosphatase HD-PTP. The specific interaction between HD-PTP and the ESCRT-I subunit UBAP1 is critical for degradation of growth factor receptors and integrins. Here, we present the structural characterization by X-ray crystallography and double electron-electron resonance spectroscopy of the coiled-coil domain of HD-PTP and its complex with UBAP1. The coiled-coil domain adopts an unexpected open and rigid conformation that contrasts with the closed and flexible coiled-coil domain of the related ESCRT regulator Alix. The HD-PTP:UBAP1 structure identifies the molecular determinants of the interaction and provides a molecular basis for the specific functional cooperation between HD-PTP and UBAP1. Our findings provide insights into the molecular mechanisms of regulation of ESCRT pathways that could be relevant to anticancer therapies.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145805 | PMC |
| http://dx.doi.org/10.1016/j.str.2016.10.006 | DOI Listing |
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