| basic FUNCTION
| involvement in apoptotic signaling, microtubule stabilization and mitotic progression |
|
inhibiting the accumulation of CCND1 and thus inducing cell cycle arrest |
|
required for prometaphase progression and may be involved in CDC20 regulation during prophase |
|
can activate BAX via MOAP1  |
|
may function as a scaffold to bring together Aurora-A and its activator(s) |
|
recruited to MOAP1/TNFRSF1A complexes |
|
implicated in prostate tumorigenesis |
|
associating with the microtubules, association that alters the microtubule dynamics and seems essential for its tumor suppressive function |
|
promotes apoptosis by signaling through the STK3 and LATS1 kinases, leading to stabilization of the YAP1/TP73 transcriptional complex |
|
tumor suppressor protein involved in death receptor-dependent apoptosis and it is localized to microtubules |
|
role for RASSF1 microtubule localization in eliciting its tumor suppressor function |
|
microtubule protein that co-localizes with tubulin and can stabilize microtubules in a paclitaxel (taxol)-like manner |
|
activates STK3 and STK4 by preventing their dephosphorylation |
|
regulates the cellular ROS levels enhanced by the RAS signaling pathway, and it may function as a tumor suppressor by suppressing DNA damage caused by activated RAS |
|
has a tumor suppressive effect as a modulator for ROS production induced by oncogenic K-Ras |
|
appear to be able to stimulate YAP1 phosphorylation by the hippo pathway, but the activation of TP73 by RASSF1 can be independent of the canonical hippo pathway |
|
is a key regulator in the fine tuning of microtubule dynamics in interphase cells and proper Golgi organization and cell polarity |
|
essential role of RASSF1 in regulating TNF signalling in cardiomyocytes |
|
RASSF1 modulates apoptosis via the Hippo and BAX pathways but also modulates the cell cycle |
|
cell cycle/microtubule effects of RASSF1A are key to its tumor suppressor function rather than its apoptotic effects |
|
two novel functions for RASSF1A in the control of DNA repair and protein acetylation |
|
as RASSF1A modulates both apoptotic DDR and DNA repair, it may play an important and unanticipated role in coordinating the balance between repair and death after DNA damage |
|
function of RASSF1 in stalled replication fork protection |
|
tumour suppressor gene epigenetically dysregulated in neuroendocrine tumour (NET) |
|
mediates transcription factor selection of YAP1 in stem cells, thereby acting as a functional "switch" between pluripotency and initiation of differentiation 9) |
|
| RASSF1/Salvador pathway is acting independently of RAS |
| a component
| heterodimerizing witn RASSF5 |
|
pro-apoptotic pathway linking KRas, RASSF1 and BAX that is specifically impaired in some human tumors |
|
component of the MST/LATS pathway |
| protein
| DNA repair protein XPA |
|
RASSF5 |
|
CDC20 and FBXO5 (for inhibition of the anaphase-promoting complex) |
|
substrate for PKC (PKC phosphorylation of RASSF1A regulates its ability to reorganize the microtubule network) |
|
RASSF1C and spliceosome component PRPF3 interacting with EMC2 |
|
interacts with STX16 at the midzone and midbody during late mitosis and AURKB is required for this interaction and for the subsequent recruitment of STX16 to the midzone and midbody |
|
interacts with the pro-apoptotic mammalian STE20-like kinases STK3 and STK4 and induces their autophosphorylation and activation |
|
SAV1 can also bind RASSF1 (RASSF1 requires the presence of Salvador for full apoptotic activity and to activate TP73) |
|
interaction of RASSF1 with RAP1A is shown to influence the effect of RASSF1 on microtubule behavior |
|
inhibits breast cancer growth, and suppresses estrogen receptor (ESR1) expression and function |
|
novel function for TP53 in the methylation of RASSF1 promoter by its interaction with DAXX |
|
XPA requires RASSF1 to exert full repair activity, and RASSF1-deficient cells exhibit an impaired ability to repair DNA |
|
RASSF1 tumor suppressor regulates BRCA2 at stalled forks |
|
MOAP1 is an integral partner to the tumor suppressor protein, (RASSF1), and functions to activate the BCL2 family pro-apoptotic protein BAX |
|
RASSF1-dependent microtubule recruitment of PRMT5, suggesting a novel role for RASSF1 in the anchoring of cytosolic PRMT5 to microtubules |
|
RASSF1 inhibits the ability of RHEB to suppress autophagy and enhance cell growth, and RHEB may complex with RASSF1 to coordinate Hippo and MTOR signaling |
|
RASSF1 limits TGFB1 induced invasion, offering a new framework on how RASSF1 affects YAP1 transcriptional output and elicits its tumor-suppressive function |
|
ANKRD1 is a YAP1 target gene that is induced by RASSF1 |
| inhibited by
| TRF3 (dependent on the activation of intracellular signaling of NF-kappaB involving the C-terminal activating regions (CTARs) of TRF3, and may facilitate its role in transformation of premalignant nasopharyngeal epithelial cells into cancer cells) |
| Other
| phosphorylated by ATM on Ser131 and is involved in the activation of both STK3 and LATS1, leading to the stabilization of TP73 |
| Other morbid association(s)
|
| Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein Function
|
|---|
| tumoral
|
|
|
| loss of function
| |
by hypermethylation in breast and thyroid carcinoma or HNSCC, pediatric tumors, clear cell and papillary renal cell carcinoma, testicular germ cell tumor, cholangiocarcinoma and prostate carcinoma | | tumoral
|
|
|
| loss of function
| |
by promoter methylation in lung and colorectal cancer, in Wilms tumor and in glioma | | tumoral
|
|
|
| loss of function
| |
by hypermethylation in medulloblastoma, hepatocellular carcinomas, cholangiocarcinomas and cervical carcinoma | | tumoral
|
| deletion
|
|
| |
in lung, breast, renal cell carcinomas (see DLEC1) and HNSCC | | tumoral
|
|
|
| loss of function
| |
frequent in pancreatic cancer and suggesting an inverse correlation between RASSF1A silencing and K-ras activation in pancreatic cancer | | tumoral
|
|
|
| loss of function
| |
hypermethylation of the promoter associated with a poor prognosis in non small cell lung cancer in patients starting cigarette smoking at an early age | | tumoral
|
|
| --low
|
| |
by promoter methylation in adenoid cystic carcinoma of the salivary gland, high-grade tumors and tumors with metastasis | | tumoral
|
|
| --low
|
| |
by DNA hypermethylation may be involved in Gallblader carcinogenesis | | tumoral
|
|
| --low
|
| |
by promoter hypermethylation in parathyroid tumours | | constitutional
|
|
| --over
|
| |
inhibits centrosome separation | | tumoral
|
|
| --low
|
| |
more pronounced in cervical tumors with lymph node metastases compared with non-metastatic ones | |
| Susceptibility
|
to lung adenocarcinoma by tobacco smoker during adolescence |
| Variant & Polymorphism
SNP
, other
| starting smoking under age 18 was significantly related to RASSF1A methylation in lung adenocarcinoma |
|
at codon 133 preferentially associated with lung adenocarcinoma risk |
| 
|
Candidate gene
Marker
Therapy target
|
| | | |
|
| Rassf1a(-/-) mice are prone to both spontaneous and carcinogen-induced tumorigenesis |
