LIM domains containing protein 1 (LIMD1)
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Function
- adapter or scaffold protein
- role in assembly of protein complexes
- role in
- cell fate determination
- cytoskeletal organization
- repression of gene transcription
- cell-cell adhesion
- cell differentiation
- proliferation & migration
- positively regulates microRNA (miRNA)-mediated gene silencing
- is essential for P-body formation & integrity
- acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases & VHL enabling efficient degradation of HIF1A
- acts as a transcriptional corepressor for SNAI1- & SNAI2/SLUG-dependent repression of E-cadherin transcription
- negatively regulates the Hippo signaling pathway & antagonizes phosphorylation of YAP1
- inhibits E2F-mediated transcription, & suppresses expression of the majority of genes with E2F1-responsive elements
- regulates osteoblast development, function, differentiation & stress osteoclastogenesis
- enhances TRAF6-facilitated activation of adaptor protein complex 1 (AP-1) & negatively regulates canonical Wnt receptor signaling pathway in osteoblasts
- may act as a tumor suppressor by inhibiting cell proliferation
- phosphorylated during mitosis
- interacts (via LIM domains) with TRAF6
- found in a complex with TRAF6, PRKCZ & SQSTM1
- interacts (via LIM domains) with SNAI2/SLUG (via SNAG domain) & SCRT1 (via SNAG domain)
- interacts with SQSTM1 & RB1
- found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 & CUL2
- interacts with EIF4E, EIF2C1, EIF2C2, DCP2, DDX6, LATS1, LATS2, EGLN1/PHD2, EGLN2/PHD1 & EGLN3/PHD3
- interacts (via LIM Zn+2-binding 2) with isoforms 1 & 3 of VHL
- interacts (via LIM domains) with SNAI1 (via SNAG domain)
Structure
- belongs to the zyxin/ajuba family
- contains 3 LIM Zn+2-binding domains
Compartment
- cytoplasm, nucleus, P-body
- cell junction, adherens junction, focal adhesion
- shuttles between cytoplasm & nucleus but is localized predominantly to the cytoplasm
- found in the nucleus but not nucleoli
- co-localizes with VCL in the focal adhesions
Expression
- ubiquitous
- expressed in normal & breast cancer tissues (at protein level)
Pathology
- down-regulation &/or elimination of its expression from the nucleus of neoplastic cells correlates strongly with poor patient prognosis & aggressive forms of breast cancer; conversely, strong nuclear localization correlates with low-tumor grade & better patient prognosis
- down-regulated in lung cancer