SGF29 and Sry pathway in hepatocarcinogenesis

Abstract

Deregulated c-Myc expression is a hallmark of many human cancers. We have recently identified a role of mammalian homolog of yeast SPT-ADA-GCN5-acetyltransferas (SAGA) complex component, SAGA-associated factor 29 (SGF29), in regulating the c-Myc overexpression. Here, we discuss the molecular nature of SFG29 in SPT3-TAF9-GCN5-acetyltransferase complex, a counterpart of yeast SAGA complex, and the mechanism through which the elevated SGF29 expression contribute to oncogenic potential of c-Myc in hepatocellularcarcinoma (HCC). We propose that the upstream regulation of SGF29 elicited by sex-determining region Y (Sry) is also augmented in HCC. We hypothesize that c-Myc elevation driven by the deregulated Sry and SGF29 pathway is implicated in the male specific acquisition of human HCCs.

Keywords: Hepatocarcinogenesis; SGF29; SPT3-TAF9-GCN5-acetyltransferase complex; Sry; c-Myc.

Figure 1

SAGA-associated factor 29 and Sry pathway in hepatocarcinogenesis. Deregulated c-Myc expression is a hallmark of many human cancers. The transcriptionally active marker of histone H3, H3K4me3/2 (red small circles depicted in left bottom of the figure), is frequently observed in the active promoter region of the E-box sequences in the c-Myc target genes. SGF29, a component of STAGA complex, which can interact with H3K4me2/3 induce the acetylation of histone at the sites of c-Myc loaded E-box leading to histone unwinding and significant induction of downstream target gene transcription. The upstream regulation of SGF29 elicited by male specific transcription factor, Sry, is also deregulated in HCC. Eventually, c-Myc target genes such as LDHA, ODC and MTA1 expression are induced, which could account for a molecular insight into the male specific acquisition of human HCC driven by the deregulated Sry and SGF29 pathway. SGF29: SAGA-associated factor 29; STAGA: SPT3-TAF9-GCN5-acetyltransferase; Sry: Sex-determining region Y; HCC: Hepatocellular carcinoma; LDH-A: Lactate dehydrogenase-A; ODC: Ornithine decarboxylase; MTA1: Metastasis-associated protein 1.