CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation

Genes Dev. 2015 Nov 1;29(21):2225-30. doi: 10.1101/gad.267708.115.


Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differentiating outer epidermis. CALML5 mRNA was up-regulated by the ZNF750 transcription factor and then stabilized by the long noncoding RNA TINCR. CALML5 knockout impaired differentiation, abolished keratohyalin granules, and disrupted epidermal barrier function. Mass spectrometry identified SFN (stratifin/14-3-3σ) as a CALML5-binding protein. CALML5 interacts with SFN in suprabasal epidermis, cocontrols 13% of late differentiation genes, and modulates interaction of SFN to some of its binding partners. A ZNF750-TINCR-CALML5-SFN network is thus essential for epidermal differentiation.

Keywords: differentiation; epidermis; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Biomarkers, Tumor / metabolism*
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism*
  • Cell Differentiation / genetics*
  • Epidermal Cells*
  • Exoribonucleases / metabolism*
  • Gene Expression Regulation, Developmental
  • Phosphoproteins / metabolism
  • Protein Binding
  • Protein Transport
  • RNA, Untranslated / metabolism*
  • Stem Cells / cytology
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins
  • YAP-Signaling Proteins


  • 14-3-3 Proteins
  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CALML5 protein, human
  • Calcium-Binding Proteins
  • Phosphoproteins
  • RNA, Untranslated
  • Transcription Factors
  • Tumor Suppressor Proteins
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • ZNF750 protein, human
  • Exoribonucleases
  • SFN protein, human

Associated data

  • SRA/SRA064531
  • SRA/SRA064538
  • SRA/SRA064547