PXD082237

PXD082237 is an original dataset announced via ProteomeXchange.

Title	Keratin 9 regulates mechanosensitive YAP1 signaling in palmoplantar epidermis
Description	The palmoplantar epidermis, in adapting to the exceptional mechanical strain it bears during locomotion, is histologically and molecularly distinct from other skin body sites. The mechanisms specifying and maintaining its unique identity remain incompletely defined. Here, we identify the type 1 keratin 9 (KRT9/K9), a protein uniquely expressed in palmoplantar epidermis, as a key modulator of mechanosensitive YAP1 signaling in response to postnatal mechanical compression. K9 loss-of-function variants driving KRT9-pEDD, a palmoplantar epidermal differentiation disorder, result in aberrant YAP1 subcellular partitioning and elevated levels of the stress-induced keratin 16 (KRT16/K16). Krt9 null mice recapitulate these molecular phenotypes as early as postnatal day 3 (P3). We further identify dynamic, YAP1-dependent regulation of Krt16/K16, upstream of and necessary for Krt9/K9 expression, during early postnatal development in situ and in response to mechanical compression of keratinocytes ex vivo, highlighting the role of mechanical stress in epidermal specification. Mechanistically, K9 interacts with the YAP1 binding protein 14-3-3σ and sequesters YAP1 in the cytoplasm, inhibiting its transcriptional activity; these functions are disrupted by KRT9-pEDD-causing variants in K9. Finally, we show that genetic or pharmacological inhibition of YAP1 ameliorates palmoplantar keratoderma in Krt9 null mice. These findings reveal a role for mechanical cues in specification and maintenance of palmoplantar skin and suggest new therapeutic interventions for inherited palmoplantar epidermal differentiation disorders (pEDDs).
HostingRepository	PRIDE
AnnounceDate	2026-08-22
AnnouncementXML	Submission_2026-08-22_13:17:24.704.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sarah Steiner
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-05 18:02:04	ID requested
⏵ 1	2026-08-22 13:17:25	announced

10.1101/2025.09.15.676359;

submitter keyword: development, keratin

Pierre A. Coulombe
contact affiliation	Dept. of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA
contact email	coulombe@umich.edu
lab head
Sarah Steiner
contact affiliation	University of Michigan Ann Arbor
contact email	sarahnst@umich.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD082237
     1. Label: PRIDE project
     2. Name: Keratin 9 regulates mechanosensitive YAP1 signaling in palmoplantar epidermis