7MRJ

Crystal structure of a novel ubiquitin-like TINCR

Summary for 7MRJ

• Entry DOI: 10.2210/pdb7mrj/pdb
• Descriptor: Ubiquitin domain-containing protein TINCR, GLYCEROL, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: novel ubiquitin-like protein, unknown function
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 24275.95

Authors

Forouhar, F.,Morgado-Palacin, L.,Brown, J.A.,Martinez, T.,Pedrero, J.M.G.,Reglero, C.,Chaudhry, I.,Vaughan, J.,Rodriguez-Perales, S.,Allonca, E.,Granda-Diaz, R.,Quinn, S.A.,Fernandez, A.F.,Fraga, M.F.,Kim, A.L.,Santos-Juanes, J.,Owens, D.M.,Rodrigo, J.P.,Saghatelian, A.,Ferrando, A.A. (deposition date: 2021-05-07, release date: 2022-03-16, Last modification date: 2023-10-25)

Primary citation

Morgado-Palacin, L.,Brown, J.A.,Martinez, T.F.,Garcia-Pedrero, J.M.,Forouhar, F.,Quinn, S.A.,Reglero, C.,Vaughan, J.,Heydary, Y.H.,Donaldson, C.,Rodriguez-Perales, S.,Allonca, E.,Granda-Diaz, R.,Fernandez, A.F.,Fraga, M.F.,Kim, A.L.,Santos-Juanes, J.,Owens, D.M.,Rodrigo, J.P.,Saghatelian, A.,Ferrando, A.A.
The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma.
Nat Commun, 14:1328-1328, 2023

PubMed Abstract: The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas.

PubMed: 36899004
DOI: 10.1038/s41467-023-36713-8

Experimental method

X-RAY DIFFRACTION (2.12 Å)