Piwi-like protein 1 (PIWIL1, HIWI)
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Function
- component of some RISC complex (RNA-induced silencing)
- role in spermatogenesis & in germ cell production, proliferation & maintenance
- when suppressed, inhibits growth of gastric cancer cells & induces cell cycle arrest in G2/M phase
- inhibits endoribonuclease DICER1 activity
- isoform 3 may be a negative developmental regulator
- interaction with endoribonuclease DICER1 via Piwi domain is regulated by HSP90AB1
Structure
- belongs to the argonaute family
- contains 1 PAZ domain
- contains 1 Piwi domain
Compartment
intracytoplasmic membrane
Alternative splicing
named isoforms=3
Expression
- expressed in most fetal & adult tissues
- expressed in testes, specifically in germline cells
- expressed in spermatocytes & spermatids during spermatogenesis
- isoform 3 is ubiquitously expressed, & specifically in CD34+ hematopoietic progenitor cells but not in more differentiated cells
- isoform 3 is down-regulated in CD34+ hematopoietic cells during differentiation
Pathology
- overexpression may cause malignant germline development
- may be associated with proliferating activity of cancer cells
- increased expression in testicular tumors originating from embryonic germ cells with retention of germ cells phenotype
- no expression in testicular tumors of somatic origin, such as Sertoli cell & Leydig cell tumors
- overexpressed in gastric cancer cells